abdelmo/pubmed-dataset · Datasets at Hugging Face

Intranasal administration of the dopaminergic agonists L-DOPA, amphetamine, and cocaine increases dopamine activity in the neostriatum: a microdialysis study in the rat.

ound that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore; intranasal administration of L-DOPA; but not of the saline vehicle; also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal L-DOPA on neostriatal dopamine was obs

8978730

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Intranasal administration of the dopaminergic agonists L-DOPA, amphetamine, and cocaine increases dopamine activity in the neostriatum: a microdialysis study in the rat.

erved only ipsilaterally but not contralaterally to the side of intranasal drug administration; it can be hypothesized that L-DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse; but may also be useful to target the brain therapeutically; as in the case of neurodegenerative brain disorders.

8978730

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Phorbol esters increase dopamine transporter phosphorylation and decrease transport Vmax.

Sodium- and chloride-coupled transport of dopamine from synapses into presynaptic terminals plays a key role in terminating dopaminergic neurotransmission. Regulation of the function of the dopamine transporter; the molecule responsible for this translocation; is thus of interest. The primary sequence of the dopamine transporter contains multiple potential phosphorylation sites; suggesting that the function of the transporter could be regulated by phosphorylation. Previous work from this laboratory has docu

8978729

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Phorbol esters increase dopamine transporter phosphorylation and decrease transport Vmax.

mented that phorbol ester activation of protein kinase C (PKC) decreases dopamine transport Vmax in transiently expressing COS cells. In the present report; we document in vivo phosphorylation of the rat dopamine transporter stably expressed in LLC-PK1; cells and show that phosphorylation is increased threefold by phorbol esters. Dopamine uptake is also regulated by phorbol esters in these cells; phorbol 12-myristate 13-acetate (PMA) reduces transport Vmax by 35%. Parallels between the time course; concentr

8978729

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Phorbol esters increase dopamine transporter phosphorylation and decrease transport Vmax.

ation dependency; and staurosporine sensitivity of alterations in transporter phosphorylation and transporter Vmax suggest that dopamine transporter phosphorylation involving PKC could contribute to this decreased transporter function. Phosphorylation of the dopamine transporter by PKC or by a PKC-activated kinase could be involved in rapid neuroadaptive processes in dopaminergic neurons.

8978729

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Kainate-evoked release of adenosine from the hippocampus of the anaesthetised rat: possible involvement of free radicals.

Using microdialysis in the hippocampus of anaesthetised rats; the concentration of extracellular adenosine was estimated to be 0.8 microM. Kainic acid (0.1-25 mM) in the perfusate evoked a concentration-dependent release of adenosine with an EC50 of 940 microM. Two 5-min pulses of 1 mM kainic acid in the perfusate increased the dialysate levels with an S2/S1 ratio of 0.52 +/- 0.03. Kainate-evoked release of adenosine was reduced significantly by 10 microM tetrodotoxin and by a kappa-receptor agonist; U50; 4

8978731

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Kainate-evoked release of adenosine from the hippocampus of the anaesthetised rat: possible involvement of free radicals.

88H (100 microM). The S2/S1 ratio was reduced by 4.5 microM 6-cyano-7-nitroquinoxaline-2;3-dione; a non-NMDA receptor antagonist; but not by the NMDA receptor blockers (+)-MK-801 (dizocilpine; 100 microM) or (+/-)-2-amino-5-phosphonopentanoic acid (1 mM); indicating a non-NMDA receptor-mediated process. The S2/S1 ratio was also reduced significantly by 10 mM ascorbic acid; 10 mM glutathione (a scavenger of hydroperoxides); and 1 mM oxypurinol (a xanthine oxidase inhibitor); indicating the possible involveme

8978731

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Kainate-evoked release of adenosine from the hippocampus of the anaesthetised rat: possible involvement of free radicals.

nt of free radicals. Neither the adenosine A1 receptor antagonist 8-cyclopentyl-1;3-dimethylxanthine (100 microM) nor the A1 adenosine receptor agonist R(-)-N6-(2-phenylisopropyl)adenosine (100 microM) affected release. Adenosine release evoked by kainic acid is therefore mediated by activation of non-NMDA receptors and may involve the propagation of action potentials and the production of free radicals.

8978731

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Altered mu-opiate receptor-G protein signal transduction following chronic morphine exposure.

This laboratory has demonstrated that the longitudinal muscle/myenteric plexus (LMMP) preparation manifests pleiotropic responses to opioid agonists. For example; the mu-selective opiate receptor agonist sufentanil can produce a naloxone-reversible increase or decrease in the electrically stimulated formation of cyclic AMP; depending on its concentration. The present study demonstrates that the sufentanil facilitation and inhibition of stimulated cyclic AMP formation are mediated via Gs- and Gi-like G prote

8978732

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Altered mu-opiate receptor-G protein signal transduction following chronic morphine exposure.

ins; respectively. Inactivation of Gi (via pertussis toxin) not only abolishes sufentanil inhibition of cyclic AMP formation but also unmasks a facilitory effect. The latter response is eliminated following treatment with cholera toxin. In tolerant/dependent LMMP tissue; previously inhibitory concentrations of sufentanil produce a facilitation of cyclic AMP formation. However; this unmasked facilitory effect is resistant to cholera toxin. Thus; although inactivation of the inhibitory signal transduction pat

8978732

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Altered mu-opiate receptor-G protein signal transduction following chronic morphine exposure.

hway (via pertussis toxin) is sufficient to unmask excitatory sufentanil effects in opiate naive preparations; this mechanism cannot explain the reversal of sufentanil inhibition to facilitation that is observed in tolerant/dependent tissue. Instead; the chronic morphine-induced emergence of a mu-opiate receptor-coupled facilitory pathway that is either not expressed or not fully manifest in opiate naive LMMP tissue is suggested.

8978732

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Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals.

Amyloid beta protein (A beta); the central constituent of senile plaques in Alzheimer's disease (AD) brain; is known to exert toxic effects on cultured neurons. The role of the voltage-sensitive Ca2+ channel (VSCC) in beta (25-35) neurotoxicity was examined using rat cultured cortical and hippocampal neurons. When L-type VSCCs were blocked by application of nimodipine; beta (25-35) neurotoxicity was attenuated; whereas application of omega-conotoxin GVIA (omega-CgTX-GVIA) or omega-agatoxin IVA (omega-Aga-IV

8978734

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Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals.

A); the blocker for N- or P/Q-type VSCCs; had no effects. Whole-cell patch-clamp studies indicated that the Ca2+ current density of beta (25-35)-treated neurons is about twofold higher than that of control neurons. Also; beta (25-35) increased Ca2+ uptake; which was sensitive to nimodipine. The 2'; 7'-dichlorofluorescin diacetate assay showed the ability of beta (25-35) to produce reactive oxygen species. Nimodipine had no effect on the level of free radicals. In contrast; vitamin E; a radical scavenger; re

8978734

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Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals.

duced the level of free radicals; neurotoxicity; and Ca2+ uptake. These results suggest that beta (25-35) generates free radicals; which in turn; increase Ca2+ influx via the L-type VSCC; thereby inducing neurotoxicity.

8978734

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A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide.

Peroxidation of membrane lipids results in release of the aldehyde 4-hydroxynonenal (HNE); which is known to conjugate to specific amino acids of proteins and may alter their function. Because accumulating data indicate that free radicals mediate injury and death of neurons in Alzheimer's disease (AD) and because amyloid beta-peptide (A beta) can promote free radical production; we tested the hypothesis that HNE mediates A beta 25-35-induced disruption of neuronal ion homeostasis and cell death. A beta indu

8978733

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A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide.

ced large increases in levels of free and protein-bound HNE in cultured hippocampal cells. HNE was neurotoxic in a time- and concentration-dependent manner; and this toxicity was specific in that other aldehydic lipid peroxidation products were not neurotoxic. HNE impaired Na+; K(+)-ATPase activity and induced an increase of neuronal intracellular free Ca2+ concentration. HNE increased neuronal vulnerability to glutamate toxicity; and HNE toxicity was partially attenuated by NMDA receptor antagonists; sugge

8978733

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A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide.

sting an excitotoxic component to HNE neurotoxicity. Glutathione; which was previously shown to play a key role in HNE metabolism in nonneuronal cells; attenuated the neurotoxicities of both A beta and HNE. The antioxidant propyl gallate protected neurons against A beta toxicity but was less effective in protecting against HNE toxicity. Collectively; the data suggest that HNE mediates A beta-induced oxidative damage to neuronal membrane proteins; which; in turn; leads to disruption of ion homeostasis and ce

8978733

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A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide.

ll degeneration.

8978733

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Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum.

Systemic administration of kainic acid (KA); an analogue of glutamic acid; causes limbic seizures and pathophysiological changes in adult rats that are very similar to human temporal lobe epilepsy. One of the earliest changes in gene expression after treatment with KA is the induction of immediate-early genes. The fos and jun families are frequently studied immediate-early genes that are induced by KA. Several groups; including ours; have recently reported that a 35-kDa Fos-related antigen (FRA) is induced

8978735

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Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum.

for a protracted time by various stimuli. It has been suggested that this FRA is delta FosB; which has a molecular mass of approximately 35 kDa. The present study characterizes the long-term expression of FRA and delta FosB after systemic treatment with KA. Immunocytochemistry and western blot analysis using an antibody that cross-reacts with all known FRAs showed that a 35-kDa FRA was induced at high levels in both the hippocampus and striatum for up to 1 month by KA. A semiquantitative PCR analysis showed

8978735

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Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum.

that delta FosB was induced by KA; but its expression lasted for only 6 h. This result was also verified by northern blot analysis. These results suggested that the 35-kDa FRA with long-term elevated levels seen with western blot analysis and immunocytochemistry is a new species of the FRA and not delta FosB. The long-term expression of FRA in both the hippocampus and striatum may be associated with the pathophysiological changes after KA administration.

8978735

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Effect of Ca2+ on in vitro astrocyte injury.

Current literature suggests that a massive influx of Ca2+ into the cells of the CNS induces cell damage associated with traumatic brain injury (TBI). Using an in vitro model for stretch-induced cell injury developed by our laboratory; we have investigated the role of extracellular Ca2+ in astrocyte injury. The degree of injury was assessed by measurement of propidium iodide uptake and release of lactate dehydrogenase. Based on results of in vivo models of TBI developed by others; our initial hypothesis was

8978737

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Effect of Ca2+ on in vitro astrocyte injury.

that decreasing extracellular Ca2+ would result in a reduction in astrocyte injury. Quite unexpectedly; our results indicate that decreasing extracellular Ca2+ to levels observed after in vivo TBI increased astrocyte injury. Elevating the extracellular Ca2+ content to twofold above physiological levels (2 mM) produced a reduction in cell injury. The reduction in injury afforded by Ca2+ could not be mimicked with Ba2+; Mn2+; Zn2+; or Mg2+; suggesting that a Ca(2+)-specific mechanism is involved. Using 45Ca2+

8978737

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Effect of Ca2+ on in vitro astrocyte injury.

; we demonstrate that injury induces a rapid influx of extracellular Ca2+ into the astrocyte; achieving an elevation in total cell-associated Ca2+ content two- to threefold above basal levels. Pharmacological elevation of intracellular Ca2+ levels with the Ca2+ ionophore A23187 or thapsigargin before injury dramatically reduced astrocyte injury. Our data suggest that; contrary to popular assumptions; an elevation of total cell-associated Ca2+ reduces astrocyte injury produced by a traumatic insult.

8978737

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Quantification of local de novo synthesis versus blood contributions to quinolinic acid concentrations in brain and systemic tissues.

The source of the neurotoxin quinolinic acid (QUIN) in brain and systemic tissues under normal and pathologic circumstances reflects either de novo synthesis from L-tryptophan and other precursors; or entry of QUIN itself from the blood. To quantify the relative contributions of blood- versus tissue-derived QUIN; [13C7]-QUIN was infused subcutaneously via osmotic pumps (0.55 microliter/h; 30 mM) in gerbils; and the fraction of QUIN in tissue (Tl; measured in tissue homogenates) derived from blood (Bl; measu

8978736

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Quantification of local de novo synthesis versus blood contributions to quinolinic acid concentrations in brain and systemic tissues.

red in serum) was calculated by the formula ([13C7]QUINTi/QUINTi)/([13C7]QUINBl/ QUINBl). In controls; blood QUIN contributed 38-49% of QUIN in brain; 70% in CSF; between 40 and 70% in kidney; heart; and skeletal muscle; but < 5% in spleen; lung; liver; and intestine. Systemic endotoxin (450 micrograms/kg) increased blood; brain; CSF; and systemic tissue QUIN levels. Notably; the relative proportion of QUIN derived from blood in brain; spleen; lung; and intestine was unchanged by endotoxin; but increased in

8978736

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Quantification of local de novo synthesis versus blood contributions to quinolinic acid concentrations in brain and systemic tissues.

kidney; heart; and skeletal muscle. In contrast; cerebral ischemic injury (10 min of bilateral carotid artery occlusion) increased regional brain QUIN concentrations at 4 days post ischemia; with a proportional increase in the amount of QUIN derived from de novo synthesis by brain tissue. In the blood and systemic tissues of postischemic gerbils; there were no changes in systemic tissue or blood QUIN levels; or changes in the relative proportions of blood- versus systemic tissue-derived QUIN. These results

8978736

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Quantification of local de novo synthesis versus blood contributions to quinolinic acid concentrations in brain and systemic tissues.

establish that the brain normally synthesizes QUIN; that the blood is a significant source of QUIN in controls and during acute systemic immune activation; and that the rate of QUIN formation by brain tissue increases in conditions of brain and systemic immune activation.

8978736

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-0.044588387, 0.008768345, 0.032113153, -0.007539323, -0.036183465, -0.023364633, 0.0057189167, 0.042870402, 0.0050019873 ]

Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy.

The pathophysiology of infantile hydrocephalus is poorly understood; and shunt treatment does not always lead to a normal neurological outcome. To investigate some of the neurochemical changes in infantile hydrocephalus and the response to shunt treatment; we have used high-resolution 1H-NMR spectroscopy to analyze extracts of cerebral cortex from H-Tx rats; which have inherited hydrocephalus with an onset in late gestation. Hydrocephalic rats and rats with shunts placed at either 4 or 12 days after birth w

8978739

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Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy.

ere studied at 21 days after birth; together with age-matched control littermates. In hydrocephalic rats there was a 46-62% reduction in the following compounds: myo-inositol; creatine; choline-containing compounds; N-acetyl aspartate; taurine; glutamine; glutamate; aspartate; and alanine. Phosphocreatine; glycine; GABA; and lactate were also reduced but not significantly. These changes are consistent with neuronal atrophy rather than ischemic damage. In hydrocephalic rats that received shunt treatment at 4

8978739

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Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy.

days; there were no significant reductions in any chemicals; indicating a normal complement of neurons. However; some compounds; particularly taurine; were elevated above control. After treatment at 12 days; N-acetyl aspartate and aspartate remained significantly reduced; suggesting continued neuronal deficiency.

8978739

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Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar affective disorder.

Findings of increased Gs alpha levels and forskolin-stimulated adenylyl cyclase activity in selective cerebral cortical postmortem brain regions in bipolar affective disorder (BD) implicate increased cyclic AMP (cAMP)-mediated signaling in this illness. Accumulating evidence suggests that intracellular levels of cAMP modulate the abundance and disposition of the regulatory subunits of cAMP-dependent protein kinase (cAMP-dPK). Thus; in the present study; we tested further whether hyperfunctional Gs alpha-lin

8978738

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Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar affective disorder.

ked cAMP signaling occurs in BD by determining [3H]cAMP binding; a measure of the levels of regulatory subunits of cAMP-dPK; in cytosolic and membrane fractions from discrete brain regions of postmortem BD brain. Specific [3H]cAMP (5 nM) binding was determined in autopsied brain obtained from 10 patients with DSM-III-R diagnoses of BD compared with age- and postmortem delay-matched controls. [3H]cAMP binding was significantly reduced across all brain regions in cytosolic fractions of BD frontal (-22%); temp

8978738

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0.038792558, -0.038579706, -0.000016837048, -0.026021345, -0.008035221, -0.06827278, 0.018371921, -0.0707738, 0.029746283, 0.0028003545 ]

Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar affective disorder.

oral (-23%); occipital (-22%) and parietal (-15%) cortex; cerebellum (-36%); and thalamus (-13%) compared with controls; but there were no differences in [3H]cAMP binding in the membrane fractions from these same regions. These results suggest that changes occur in the cAMP-dPK regulatory subunits in BD brain; possibly resulting from increased cAMP signaling. The possibility that antemortem lithium and/or other mood stabilizer treatment may contribute to the above changes; however; cannot be ruled out.

8978738

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-0.08518204, -0.040909797, -0.09414857, 0.034238268, -0.022256209, -0.047554635, 0.035225656, 0.011701856, -0.02339037, -0.04726109, 0.014330437, -0.057855472, 0.035412457, -0.011314907, 0.01705242, 0.05956338, -0.01601166, -0.08069877, 0.011815272, 0.058762796, -0.27838942, -0.006614818, 0.02234961, -0.053212088, 0.0020798482, 0.070397936, 0.0011224842, -0.04509951, -0.080431916, 0.051103886, 0.070985034, 0.005090374, 0.084541574, 0.044725906, 0.0045766667, 0.02724651, 0.07013108, -0.07712284, 0.028394014, -0.016718844, 0.03992241, -0.014410496, 0.14090262, 0.014090262, -0.00765224, -0.034264956, -0.012642541, 0.010074004, 0.015691428, 0.026646074, 0.021322196, 0.012042103, 0.07226597, 0.017986434, -0.016732186, 0.09233391, 0.0028754275, -0.009099961, 0.061111175, -0.0044332286, -0.003023869, 0.048088357, -0.044966083, 0.011008018, 0.08016505, 0.02348377, -0.008946516, 0.027753547, 0.008292707, -0.007939115, -0.01787969, 0.0038995068, 0.0048301844, 0.012876044, 0.03127611, 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Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats.

The role of gamma-aminobutyric acid (GABA) modulation of septohippocampal cholinergic neurons in kindling was investigated. Hippocampal acetylcholine release was evaluated with the microdialysis technique in freely moving rats either after acute administration of isoniazid (an inhibitor of GABA synthesis) or pentylenetetrazole (PTZ) (a blocker of the GABAA receptor-associated Cl- channel) or after chronic administration of PTZ. Short-term treatment with PTZ (5-50 mg/kg; i.p.) or isoniazid (150-250 mg/kg; s.

8978740

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Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats.

c.) increased hippocampal acetylcholine release in a dose-dependent manner. In contrast; the basal concentration of acetylcholine in the dialysate from the hippocampus of rats chronically treated with PTZ (kindled animals) was significantly reduced relative to that of vehicle-treated rats (2.39 +/- 0.21 vs. 4.2 +/- 0.31 pmol per 20-min sample; p < 0.01). Moreover; the release of acetylcholine was markedly more sensitive to the effect of a challenge injection of PTZ (10 or 20 mg/kg; i.p.) in kindled rats tha

8978740

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Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats.

n in naive rats or rats chronically treated with vehicle. Abecarnil; a selective benzodiazepine receptor agonist with marked anticonvulsant activity; was administered together with chronic PTZ to evaluate whether persistent activation of GABAA receptors and suppression of seizures during kindling might affect the sensitivity of septohippocampal cholinergic neurons to a challenge dose of PTZ. Abecarnil (1 mg/kg; i.p.) administered 40 min before each PTZ injection neither antagonized the decrease in basal ace

8978740

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-0.0054995213, 0.041031327, 0.03976068, 0.019443555, -0.03758999, 0.10138708, 0.02191867 ]

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0.025480123, -0.05111908, -0.0055162814, 0.04097998, 0.039735757, 0.01948402, -0.03756498, 0.10133809, 0.021919524 ]

Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats.

tylcholine release (2.26 +/- 0.19 pmol per 20-min sample) nor prevented the development of kindling. In contrast; abecarnil prevented the chronic PTZ-induced increase in the sensitivity of acetylcholine release to a challenge dose of PTZ. These results provide novel in vivo data concerning the role of hippocampal acetylcholine function in the development of kindling and potentially in the learning and memory deficits associated with this phenomenon.

8978740

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Generation of reactive oxygen species by tyrosine hydroxylase: a possible contribution to the degeneration of dopaminergic neurons?

It has been suggested that idiopathic parkinsonism; characterized by a loss of dopaminergic neurons of the nigrostriatal pathway; is due to the intracellular generation of reactive oxygen species; generated by a nonenzymatic or enzymatic partial reduction of dioxygen. Based on in vitro studies of the iron-containing monooxygenase tyrosine hydroxylase (TH); evidence is presented that this enzyme system may also contribute to such an oxidative stress. Thus; the purified and Fe(2+)-reconstituted recombinant hu

8978742

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Generation of reactive oxygen species by tyrosine hydroxylase: a possible contribution to the degeneration of dopaminergic neurons?

man enzyme shows a time- and temperature-dependent partial uncoupling of the hydroxylation of L-tyrosine with the natural cofactor (6R)-tetrahydrobiopterin; resulting in the formation of H2O2. The degree of uncoupling of the hydroxylation reaction is significantly higher when certain substrate analogues; notably the 7-substituted isomer (7-tetrahydrobiopterin) of the natural cofactor; is used. In the presence of H2O2 and Fe2+; the addition of TH increases the production of the highly reactive.OH radical; pr

8978742

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Generation of reactive oxygen species by tyrosine hydroxylase: a possible contribution to the degeneration of dopaminergic neurons?

obably via a Fenton type of reaction. It is not clear whether this in vitro reaction can mediate cellular injury in vivo. However; it is known that the distribution of TH in the central and peripheral nervous system often corresponds to that of the neuronal degeneration in idiopathic parkinsonism; a finding that is compatible with a pathogenetic effect of TH.

8978742

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Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal death: role of cyclic GMP.

Somatostatin (SRIF) exerts a modulatory function on neuronal transmission in the CNS. It has been proposed that a reduction of calcium currents is the major determinant of the inhibitory activity of this peptide on synaptic transmission. Because the neurotoxicity induced by activation of the NMDA subtype of glutamate receptor is mediated through excessive Ca2+ influx; we investigated whether SRIF counteracted NMDA-induced neuronal cell death. Neurons from embryonic rat cerebral cortex were cultured for 7-10

8978741

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Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal death: role of cyclic GMP.

days and then exposed to 0.5 and 1 mM NMDA for 24 h. The neuronal viability; as assessed by the colorimetric method; decreased by 40 and 60%; respectively; compared with the control condition. Morphological and biochemical evidence indicated that cell death occurred by necrosis and not through an apoptotic mechanism. SRIF (0.5-10 microM); simultaneously applied with excitatory amino acid; significantly reduced in a dose-dependent manner the neurotoxic effect of NMDA but not that of KA (0.25-0.5 mM). GABA (

8978741

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0.01470785, 0.022465548, -0.026781261, -0.027906524, 0.00018275183, -0.010815764, -0.024941126, -0.002991876, 0.0075525013, -0.017712966, 0.09319826, 0.029733423 ]

Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal death: role of cyclic GMP.

10 microM) partially protected neurons to a similar extent from NMDA- or KA-induced toxicity. SRIF type 2 receptor agonists; octreotide (SMS 201-995; 10 microM) and vapreotide (RC 160; 10 microM); did not influence the NMDA-dependent neurotoxicity. The intracellular mechanism involved in SRIF neuroprotection was investigated. Pertussin toxin (300 ng/ml); a G protein blocker; antagonized the protective effect of SRIF on NMDA neurotoxicity. Furthermore; the neuroprotective effect of SRIF was mimicked by dibut

8978741

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Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal death: role of cyclic GMP.

yryl-cyclic GMP (10 microM); a cyclic GMP analogue; whereas 8-(4-chlorphenylthio)-cyclic AMP (10 microM); a cyclic AMP analogue; was ineffective. The cyclic GMP content was increased in a dose-dependent manner by SRIF (2.5-10 microM). Finally; both specific (Rp-8-bromoguanosine 3';5'-monophosphate; 10 microM) and nonspecific [1-(5 isoquinolinylsulfonyl)-2-methylpiperazine (H7); 10 microM] cyclic GMP-dependent protein kinase (cGMP-PK) inhibitors did not interfere with NMDA toxicity but substantially reduced

8978741

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Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal death: role of cyclic GMP.

SRIF neuroprotection. Our data suggest a selective neuroprotective role of SRIF versus NMDA-induced nonapoptotic neuronal death in cortical cells. This effect is likely mediated by cGMP-PK presumably by regulation of the intracellular Ca2+ level.

8978741

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Inhibition of beta-amyloid formation by haloperidol: a possible mechanism for reduced frequency of Alzheimer's disease pathology in schizophrenia.

Several reports have suggested that the frequency of Alzheimer's disease (AD) neuropathology is significantly reduced in elderly individuals with schizophrenia (SZ); and it has been proposed that medications used for treatment of SZ may be responsible. A central event in AD pathology is the formation of beta-amyloid (A beta) peptide; which is derived by enzymatic processing of its precursor protein. Haloperidol; an antipsychotic medication commonly used in the treatment of SZ; can act as an inhibitor of sel

8978743

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Inhibition of beta-amyloid formation by haloperidol: a possible mechanism for reduced frequency of Alzheimer's disease pathology in schizophrenia.

ect proteinases; hence; we examined the ability of this compound to inhibit A beta formation by cultured cells. Haloperidol and; to a lesser extent; droperidol inhibited A beta in a dose-dependent manner. These results may explain the apparent reduction of AD neuropathological changes in elderly patients with SZ as well as provide a possible mechanism for this difference.

8978743

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-0.0006937167, 0.024864918, -0.0010847057, 0.020351224, -0.023320759, 0.032651704, 0.018331937, -0.047037456, -0.03600398, 0.071849585, 0.015599964 ]

Portacaval shunting and hyperammonemia stimulate the uptake of L-[3H] arginine but not of L-[3H]nitroarginine into rat brain synaptosomes.

Elevated activities of nitric oxide synthase (NOS) have been reported previously in the brains of portacaval-shunted (PCS) rats; a model of chronic hepatic encephalopathy (HE). As L-arginine availability for nitric oxide synthesis depends on a specific uptake mechanism in neurons; we studied the kinetics of L-[3H]-arginine uptake into synaptosomes prepared from the brains of PCS rats. Results demonstrate that L-arginine uptake is significantly increased in cerebellum (60%; p < 0.01); cerebral cortex (42%; p

8978744

[ -0.024419395, -0.011136098, 0.0008489607, 0.04022332, 0.013830099, 0.02031171, 0.05011911, 0.04187706, -0.043797538, -0.004357748, -0.021685382, -0.046064768, 0.005661405, 0.10269216, -0.013289966, -0.032888163, -0.016110666, 0.0105759585, -0.055853866, -0.012069663, -0.022378888, -0.06241549, 0.043504134, 0.006048168, -0.020911857, -0.0056814104, -0.04550463, 0.007915298, -0.072337955, -0.17401654, 0.04745178, -0.032408044, -0.02221885, -0.064069234, -0.042063776, 0.023952613, -0.0070484164, 0.0069083814, -0.024032632, 0.0529198, 0.05273309, 0.023312453, -0.028086971, 0.020031638, 0.03926308, 0.011082751, -0.0670033, -0.05305317, 0.054733586, -0.022378888, 0.03870294, -0.008955556, -0.003335828, 0.0479319, 0.021952115, -0.003940978, 0.022112155, 0.03531543, -0.04374419, 0.02245891, -0.017671052, 0.019764906, -0.12589791, 0.017617706, 0.10562622, -0.061668642, -0.052999824, -0.018177846, -0.011056078, 0.009715745, -0.08364743, 0.0040243324, 0.023032384, -0.040996842, 0.01971156, -0.03806278, -0.017057568, -0.01379009, 0.015510517, -0.010762672, 0.054626893, -0.020671798, 0.026513249, 0.019138085, 0.027393466, 0.010542617, -0.015163764, -0.016043983, -0.0013820097, 0.006935055, -0.022632284, -0.029180577, 0.05969482, -0.034301847, -0.044597737, 0.041423615, 0.04041003, -0.0057114176, -0.06204207, 0.37940085, 0.012129677, 0.013610045, -0.08556791, 0.017631043, -0.025619693, -0.047398433, -0.014550279, -0.008608803, 0.019764906, 0.055533785, 0.03699585, 0.017991133, 0.043984253, 0.0098224385, -0.040063277, 0.011376157, 0.0018321214, -0.025539674, 0.018271202, 0.051639486, -0.038249496, 0.033715036, 0.05214628, 0.024566097, 0.028913844, -0.0066316463, -0.045637995, 0.07361827, 0.04675827, 0.006401589, 0.02928727, 0.026579931, -0.024712801, 0.05404008, 0.033554997, -0.0013478346, 0.05094598, -0.032434717, 0.029260596, 0.048278652, -0.033875074, 0.0016812506, -0.039209735, -0.083060615, -0.016750826, 0.055213705, 0.04923889, -0.04161033, 0.0212186, 0.040516723, 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-0.04033001, -0.061668642, 0.03440854, -0.05428014, 0.033394955, 0.019444827, 0.05185287, -0.03051424, 0.00814869, 0.025539674, -0.07505863, 0.009489022, 0.017430993, -0.0066349804, 0.03600894, -0.043850884, -0.0623088, 0.013490016, 0.032434717, -0.23813911, 0.0030991025, 0.026233178, 0.02960735, -0.057400916, -0.020178342, -0.010095839, -0.015297131, -0.014470259, 0.003644238, 0.045664668, 0.04195708, 0.07697911, 0.03600894, -0.02984741, -0.047105026, 0.07719249, 0.02734012, 0.035022028, -0.04510453, 0.006151527, -0.0048111943, 0.13912787, -0.000062515515, -0.0052079596, 0.015230447, -0.025979782, -0.005948143, 0.016617458, -0.0015403824, -0.03307488, -0.0054580215, 0.08039329, -0.03528876, 0.05388004, 0.044064272, -0.10866697, 0.0049612317, -0.027086724, 0.012976554, -0.018911362, -0.012976554, -0.052199624, -0.06092179, 0.053773347, -0.05225297, -0.019258114, 0.010475934, -0.052493032, 0.008942219, -0.011949633, 0.00806867, -0.012743163, -0.020098323, -0.033901747, 0.008895542, 0.014696982, 0.017057568, 0.059588123, -0.030114142, 0.008895542, 0.08551456, -0.019618204, 0.094796866, 0.022592274 ]

Portacaval shunting and hyperammonemia stimulate the uptake of L-[3H] arginine but not of L-[3H]nitroarginine into rat brain synaptosomes.

< 0.01); hippocampus (56%; p < 0.01); and striatum (51%; p < 0.01) of PCS rats compared with sham-operated controls. Hyperammonemia in the absence of portacaval shunting also stimulated the transport of L-[3H]arginine; kinetic analysis revealed that the elevated uptake was due to increased uptake capacity (Vmax) without any change in affinity (Km). Incubation of cerebellar synaptosomes with ammonium acetate for 10 min caused a dose-dependent stimulation of L-[3H]arginine uptake. Neither portacaval shunting

8978744

[ -0.018731335, 0.01661307, 0.033918906, 0.024153564, 0.03844853, 0.023327574, 0.04622883, -0.012090105, -0.03120113, 0.007047565, -0.0005029217, -0.028962962, 0.042685065, 0.06432069, 0.013595539, -0.011170857, -0.023500765, 0.016812906, -0.038981427, 0.04814726, 0.004622883, -0.01875798, 0.04452356, -0.011264114, 0.040793277, 0.046921596, 0.055314727, 0.03887485, -0.06330819, -0.12395188, 0.034611672, 0.025192713, -0.02160898, -0.062775284, -0.02922941, -0.013442331, -0.046841662, 0.012749565, -0.0040233736, -0.012862805, 0.043004803, 0.005225723, -0.013135916, -0.0015495651, 0.0580325, 0.042258747, -0.059045006, 0.0057186526, 0.07369968, -0.05099826, -0.07577798, -0.029575793, 0.018891204, 0.082865514, 0.043964017, 0.009518876, 0.045482773, -0.0072673853, -0.021089405, 0.014294967, 0.030641587, 0.028616577, -0.13333087, -0.022807999, 0.15240858, -0.04177914, -0.0062815254, -0.07657732, 0.031893894, -0.04327125, -0.017425738, -0.009891904, 0.017558962, 0.036103785, -0.04934628, 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-0.026618214, -0.027097821, 0.03176067, -0.111801825, -0.028669868, 0.02741756, -0.093576744, 0.07609772, -0.033252783 ]

Portacaval shunting and hyperammonemia stimulate the uptake of L-[3H] arginine but not of L-[3H]nitroarginine into rat brain synaptosomes.

nor hyperammonemia had any significant effect on the synaptosomal uptake of NG-nitro-L-[3H]arginine. These studies demonstrate that increased NOS activity observed in experimental HE may result from increased availability of L-arginine resulting from a direct stimulatory effect of ammonia on L-arginine transport.

8978744

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Key residues defining the mu-opioid receptor binding pocket: a site-directed mutagenesis study.

Structural elements of the rat mu-opioid receptor important in ligand receptor binding and selectivity were examined using a site-directed mutagenesis approach. Five single amino acid mutations were made; three that altered conserved residues in the mu; delta; and kappa receptors (Asn150 to Ala; His297 to Ala; and Tyr326 to Phe) and two designed to test for mu/delta selectivity (Ile196 to Val and Val202 to Ile). Mutation of His297 in transmembrane domain 6 (TM6) resulted in no detectable binding with [3H]DA

8978745

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0.070944965, 0.004973338, -0.03597847, -0.020852067, 0.050359208, 0.030172914, -0.03595184, 0.03917419, 0.0044507044, -0.042556327, 0.083940886, 0.047136858, -0.06748293, 0.014447314, 0.0041344617, 0.05773599, -0.019094422, -0.008754939, -0.03621815, 0.01717699, 0.0133820735, -0.24585733, 0.025192918, 0.072329774, 0.020266185, -0.006215008, 0.086603984, 0.026377998, -0.015499238, -0.03999975, 0.097149864, -0.015832124, -0.0036251438, 0.05363482, -0.065139405, -0.022037147, 0.035259433, 0.042023707, -0.045512367, 0.06742968, -0.06705684, -0.0043175495, -0.03355505, 0.15531194, 0.013888063, -0.0052163457, 0.03416756, 0.0048268675, 0.0064879754, -0.06359481, -0.045405842, 0.026178265, -0.06604486, 0.05869471, -0.030599011, 0.00904788, 0.015339452, 0.01664437, 0.042050336, 0.003854836, -0.021544473, 0.016804157, 0.029587032, -0.10439349, -0.05256958, 0.03999975, -0.053288616, -0.024593722, -0.021211585, -0.013581806, -0.057363156, -0.023488535, -0.090172544, 0.040718786, -0.019786827, 0.060452353, 0.01836207, -0.0248334, -0.031584356, -0.0022519834, 0.029640295, 0.024207572, 0.02820222, -0.011810845, 0.11738942, -0.0018075786 ]

Key residues defining the mu-opioid receptor binding pocket: a site-directed mutagenesis study.

MGO (3H-labeled D-Ala2; N-Me-Phe4; Gly-ol5-enkephalin); [3H]bremazocine; or [3H]ethylketocyclazocine. Mutation of Asn150 in TM3 produces a three- to 20-fold increase in affinity for the opioid agonists morphine; DAMGO; fentanyl; beta-endorphin1-31; JOM-13; deltorphin II; dynorphin1-13; and U50;488; with no change in the binding of antagonists such as naloxone; naltrexone; naltrindole; and nor-binaltorphamine. In contrast; the Tyr326 mutation in TM7 resulted in a decreased affinity for a wide spectrum of mu;

8978745

[ -0.034312993, -0.0094465185, 0.028019665, -0.06575351, 0.03799498, 0.040945794, 0.07881021, 0.0050300914, 0.046821304, 0.008036396, -0.0047722217, -0.098238565, 0.043139316, 0.027993552, 0.022953669, 0.020525124, -0.05415917, -0.022000529, -0.068782665, 0.0146104405, 0.06664137, -0.06355999, 0.022888385, -0.025055796, 0.04118081, 0.040763, -0.012939184, -0.014897688, -0.039483443, -0.07546769, -0.01730012, 0.0068417075, 0.07149845, -0.024703266, -0.007840545, 0.021295467, -0.013670359, 0.014767121, 0.06544015, -0.063664444, -0.027105696, -0.044314418, -0.004847298, -0.05447253, 0.02108656, -0.03969235, -0.045202274, 0.026635656, 0.02069486, -0.028306913, -0.052122325, -0.036323722, 0.035174735, 0.04663851, 0.040789112, 0.09865638, 0.054054715, -0.004530673, 0.030474324, 0.058755122, 0.04838811, 0.011463777, -0.15218882, 0.0319889, 0.01630781, 0.0075598257, 0.027732419, -0.061314236, -0.02089071, 0.052200664, 0.0023028743, 0.0063553457, -0.029482014, 0.014923802, -0.016007507, 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0.022444457, -0.0403713, -0.052070096, -0.016764795, -0.04324377, -0.04507171, -0.0046220697, -0.008800212, 0.029038088 ]

[ -0.03420784, -0.009492023, 0.02807132, -0.06585662, 0.037941977, 0.040944956, 0.07891305, 0.0050822143, 0.04674201, 0.008029703, -0.004700314, -0.09828879, 0.043216776, 0.028045207, 0.022927087, 0.020550817, -0.054210287, -0.021921743, -0.068885714, 0.014557917, 0.06669223, -0.06355869, 0.02291403, -0.025094453, 0.041206084, 0.040814392, -0.012919335, -0.014923497, -0.039456524, -0.07546615, -0.017260598, 0.0068154554, 0.07144477, -0.024728874, -0.007873026, 0.021360315, -0.013657023, 0.014779876, 0.065438814, -0.06355869, -0.027052918, -0.044261288, -0.004788445, -0.05441919, 0.021020848, -0.039613202, -0.04517524, 0.026661225, 0.020681381, -0.02835856, -0.05212126, -0.036192417, 0.03520013, 0.046611447, 0.04078828, 0.09860214, 0.054105837, -0.004520788, 0.030499814, 0.058753923, 0.048361007, 0.011470072, -0.15239462, 0.031962134, 0.016281364, 0.0075270305, 0.027757965, -0.061312985, -0.020864172, 0.0521996, 0.0022391772, 0.0064596673, -0.029429188, 0.01491044, -0.016020237, 0.0012542331, 0.043060098, -0.078077435, -0.00727243, -0.028123545, -0.021817291, -0.03198825, -0.025120568, -0.021686727, 0.057552733, 0.03245828, -0.07019135, -0.017639235, 0.0017365048, -0.017338935, -0.050058343, 0.044574644, 0.0043184133, 0.020276632, -0.03710637, 0.02262679, -0.003815741, -0.017025582, -0.0341295, 0.24337181, -0.015289077, 0.057552733, 0.012605981, -0.043477904, -0.035330694, -0.0043869596, 0.0029556488, -0.04856991, -0.0187882, 0.02222204, -0.023410175, 0.00081888284, 0.050058343, -0.10037781, -0.0010281936, -0.017782854, 0.08188991, -0.008349585, -0.058231667, 0.056664895, 0.005473907, 0.034155615, -0.001099188, -0.019884938, -0.0068807374, -0.024454689, 0.02203925, 0.13422008, -0.04556693, -0.009472438, 0.045749724, -0.019963278, -0.059432857, -0.029559752, 0.033790033, -0.009642172, -0.041493326, -0.063036434, 0.029403076, -0.035435144, -0.010353747, -0.15375249, -0.022391774, -0.020668324, -0.021934798, 0.031074299, -0.08047982, 0.041963357, 0.017717572, 0.04809988, 0.00672406, 0.081628785, -0.015380472, -0.0922306, 0.023044595, -0.023841036, -0.024298012, 0.039273735, -0.021255864, -0.02075972, 0.032641068, -0.07165367, 0.0028822063, -0.0067893425, -0.019976335, -0.096617565, 0.031204863, 0.056351542, -0.0020057936, -0.031335425, -0.0014296789, 0.048778813, -0.07708515, -0.034312293, 0.11646333, -0.011189358, 0.03091762, 0.00763801, 0.023266554, 0.0050463094, -0.044496305, -0.03410339, 0.08157656, -0.007722877, 0.004886368, 0.0063225753, 0.015419641, 0.008160267, 0.018109266, -0.031596556, -0.0237627, 0.053374678, 0.044261288, 0.04400016, -0.036819126, -0.0012844261, 0.041467216, 0.024807213, 0.019832714, -0.025799502, 0.09494634, -0.039769877, 0.015732996, 0.016085519, -0.046715897, -0.026817903, 0.033502795, -0.04178057, 0.025368638, 0.04400016, -0.008323473, -0.023279611, 0.03687135, 0.016960299, -0.041101635, -0.009230894, 0.031022072, 0.04264229, 0.00010853155, 0.03924762, -0.034051165, -0.04415684, -0.059276182, -0.30228242, 0.07886082, 0.11238973, -0.068781264, 0.007938308, 0.035330694, -0.004520788, -0.0037537229, 0.07593618, 0.06794565, 0.039848216, 0.0025753803, -0.027601289, 0.05196458, -0.022052307, -0.006254029, 0.067841195, -0.048961602, 0.035174016, -0.013160879, -0.0075139743, -0.001312171, -0.024493858, -0.010765024, 0.033868372, -0.014349014, 0.1799698, 0.054523643, 0.011796482, -0.037811413, 0.021817291, 0.008591129, -0.039769877, -0.055098124, -0.011581051, 0.017534783, -0.053583577, 0.036819126, -0.024402464, -0.04178057, -0.020159123, 0.004788445, 0.0010469623, -0.010046921, 0.012945448, -0.059223957, -0.043843485, -0.013350197, -0.01966298, -0.04864825, -0.0550459, 0.0016369496, 0.038098656, 0.06914684, 0.060477372, 0.05770941, -0.02455914, 0.034808435, 0.0049875556, -0.026791789, -0.009785793, -0.05697825, -0.016255252, -0.064080946, -0.012410134, 0.017952587, 0.008982822, -0.015850503, 0.018905707, -0.027966868, -0.03721082, 0.05551593, 0.0042270184, -0.009909828, 0.04682035, 0.08685136, 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-0.01348729, 0.022457056, -0.040292136, -0.05204292, -0.016712228, -0.043269, -0.045044675, -0.004703578, -0.008786975, 0.029063608 ]

Key residues defining the mu-opioid receptor binding pocket: a site-directed mutagenesis study.

delta; and kappa agonists and antagonists. Altering Val202 to Ile in TM4 produced no change on ligand affinity; but Ile196 to Val resulted in a four- to fivefold decreased affinity for the mu agonists morphine and DAMGO; with no change in the binding affinities of kappa and delta ligands.

8978745

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Nociceptin/orphanin FQ metabolism: role of aminopeptidase and endopeptidase 24.15.

The endogenous opioid receptor-like1 (ORL1) ligand; nociceptin/orphanin FQ (FGGFTGARKSARKLANQ); a heptadecapeptide structurally resembling dynorphin A; has recently been identified. The wide distribution of ORL1 mRNA and nociceptin/orphanin FQ precursor in the CNS; particularly in the limbic system regions and in several areas known to be involved in pain perception; suggests that nociceptin/orphanin FQ is potentially endowed with various central functions. In general; activation and/or inactivation of regu

8978746

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Nociceptin/orphanin FQ metabolism: role of aminopeptidase and endopeptidase 24.15.

latory peptides occur through the action of cell surface peptidases. The physiological mechanisms under which nociceptin/orphanin FQ is metabolized should lead to a better understanding of its physiological functions. Mouse brain cortical slices were incubated in medium containing the heptadecapeptide in the presence or in the absence of peptidase inhibitors. The critical sites of enzymatic cleavage are Phe1-Gly2; Ala7-Arg8; Ala11-Arg12; and Arg12-Lys13 bonds. The major role played by metallopeptidases was

8978746

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0.022444457, -0.0403713, -0.052070096, -0.016764795, -0.04324377, -0.04507171, -0.0046220697, -0.008800212, 0.029038088 ]

Nociceptin/orphanin FQ metabolism: role of aminopeptidase and endopeptidase 24.15.

confirmed by the complete protection of metabolism in the presence of EDTA. Aminopeptidase N and endopeptidase 24.15 are the two main enzymes involved in nociceptin/orphanin FQ metabolism; whereas endopeptidase 24.11 (involved in enkephalin [YGGFM(L)] catabolism) does not appear critically involved in nociceptin/orphanin FQ metabolism. The physiological relevance of aminopeptidase N and endopeptidase 24.15 in the heptadecapeptide metabolism remains to be determined.

8978746

[ -0.006993411, -0.005589456, 0.04880228, -0.0004531546, 0.008548968, 0.02834276, -0.008832395, 0.06633524, 0.008621472, -0.041657265, 0.018758953, -0.07614315, -0.008773073, 0.0035790973, -0.020209048, 0.0145273125, -0.060060285, 0.025020724, -0.031374775, 0.023386072, 0.06390963, -0.034327697, 0.034855004, -0.040919036, 0.0020630893, 0.010196802, -0.060007557, -0.025798503, 0.00728343, -0.16494168, 0.026299445, -0.01889078, 0.032930333, -0.018785318, 0.009629947, -0.028184569, -0.07160831, 0.0061793807, -0.0349341, -0.008951039, 0.06891905, -0.005945388, 0.03050472, 0.027657261, 0.007197743, 0.049566872, -0.024348408, 0.032139372, 0.012734468, 0.012510362, 0.0088983085, -0.038994364, 0.000837924, 0.1055669, 0.02627308, 0.021342758, 0.04329192, 0.02135594, -0.06037667, 0.0045579113, -0.047563106, 0.011976464, -0.13952547, 0.031902082, 0.033484004, 0.014105467, 0.04880228, -0.048644084, 0.030425623, -0.0020976937, -0.041868187, 0.046218473, -0.06876086, 0.065280624, -0.0070922812, 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0.010012245, -0.061378554, -0.07324296, -0.008008477, 0.004422789, -0.038651615, 0.013538611, 0.05663279, -0.011040494, -0.0016453632, 0.0030122423, 0.04748401, 0.015199629, 0.00086758507, -0.017322041, -0.021540498, 0.0011847933, -0.04816951, -0.005648778, -0.01854803, -0.26766112, 0.0449793, -0.001886771, 0.020380422, -0.046640318, 0.031137489, 0.090696834, -0.034960464, -0.0036351238, 0.04260642, 0.018653492, 0.0035955757, 0.07730323, 0.0077118673, 0.035013195, 0.04326555, 0.051887024, 0.04600755, -0.024348408, -0.02258193, 0.06100944, 0.0077711893, 0.12739742, -0.049619604, 0.019563096, 0.013077218, 0.026760839, 0.00041978594, 0.015463282, -0.053099833, -0.038836174, 0.05157064, 0.019062154, 0.02189643, 0.017453868, -0.025271196, 0.0039482126, -0.0024783437, 0.012233526, -0.0052862545, -0.01919398, 0.02126366, -0.07682865, -0.032403026, 0.08547649, -0.046956703, -0.0664407, 0.00349341, 0.052730717, 0.008305088, -0.04856499, -0.03095293, 0.003684559, 0.0005306028, -0.014540495, -0.018587578, 0.008509419, -0.041472707, 0.030241067, 0.04827497, 0.031612065, 0.0017055091, 0.008443506, 0.06549155, -0.025772138 ]

Corticosteroid modulation of signal transduction in the CATH.a cell line.

Noradrenergic neuronal networks originating in the locus coeruleus have been implicated in the stress response. In order to study this system in vitro; we have employed a locus coeruleus-like cell line; CATH.a; and have determined the effect of dexamethasone on receptor-mediated second messenger responses. The CATH.a cell line produced increases in intracellular cyclic AMP conversion in response to corticotrophin-releasing factor (EC50 = 6.93 +/- 1.26 nM; maximum conversion = 4.11 +/- 0.20%) and vasoactive

8978747

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-0.006039797, 0.023588708, -0.04754889, 0.041446075, 0.033167474, 0.04797343, 0.011091203, -0.012570472, 0.07885899, -0.012205631 ]

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Corticosteroid modulation of signal transduction in the CATH.a cell line.

intestinal polypeptide (EC50 = 240 +/- 40 nM; maximum conversion = 8.92 +/- 1.24%). Forskolin (10 microM) increased conversion from 0.48 +/- 0.05 to 6.39 +/- 0.38%. The alpha 2-adrenoceptor agonist 5-bromo-N-(4;5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) inhibited the forskolin response with an IC50 of 6.76 +/- 0.11 nM. Carbachol increased total 3H-labelled inositol phosphate accumulation to a maximum of 3.01 +/- 0.79 fold basal (EC50 = 7.94 +/- 0.14 microM). Bradykinin produced a maximum 1.81 +

8978747

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Corticosteroid modulation of signal transduction in the CATH.a cell line.

/- 0.05 fold basal stimulation of phosphoinositide hydrolysis (EC50 = 9.12 +/- 0.16 nM). Both carbachol and bradykinin increased intracellular Ca2+ concentration probably via a combination of mobilisation of intracellular stores and gating of extracellular Ca2+. Incubation for 24 h with the glucocorticoid receptor agonist; dexamethasone (1 microM); significantly potentiated the receptor-mediated phosphoinositide responses to all the agents tested; however; of the receptor-mediated increases in cyclic AMP co

8978747

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-0.050521966, -0.019204179, -0.023432015, 0.037533633, -0.12808087, 0.016699286, 0.017375208, -0.010788268, 0.028494813, 0.017017368, 0.04524711, 0.035943225, -0.012782905, -0.043418143, -0.04691704, -0.06520674, -0.01773305, -0.009688237, -0.006712848, -0.24789162, -0.04021082, 0.023060918, 0.0323383, -0.025088688, 0.053331688, 0.06419948, 0.0035187781, 0.034008227, -0.00009996999, -0.021523524, -0.05836798, 0.052536484, -0.012577478, -0.04768574, 0.028203238, 0.030456316, -0.017202916, -0.07952041, -0.048719503, 0.056512505, -0.029396044, 0.08487479, 0.0077201063, 0.027726116, 0.0029091216, -0.020715067, 0.019946368, 0.0074086515, -0.0055929353, -0.018965617, 0.008058068, 0.02135123, -0.049806282, -0.028839402, 0.020781333, 0.025936907, -0.006699594, 0.022689823, 0.0074947984, -0.03954815, 0.024757354, -0.07395398, -0.045300126, 0.051343676, -0.014353434, -0.06250304, -0.022106674, -0.0028395413, -0.033160012, -0.039336096, -0.0040721074, -0.019588528, 0.017388463, 0.038699932, 0.059004143, 0.03763966, 0.0068122484, 0.019469246, -0.019204179, 0.044239853, -0.06404044, 0.009926798, 0.10274037, -0.03432631 ]

Corticosteroid modulation of signal transduction in the CATH.a cell line.

nversion; only the vasoactive intestinal polypeptide response was potentiated. These results show that the CATH.a cell line displays some of the properties expected of locus coeruleus neurons and that glucocorticoid receptor stimulation selectively modulates receptor-mediated increases in second messenger formation.

8978747

[ -0.064953856, -0.0012796255, -0.086729065, -0.020620061, -0.015893247, -0.023156077, 0.03858461, 0.029184092, -0.0038372169, -0.042089887, 0.030591514, -0.06606917, 0.00009745527, 0.031972382, 0.008391422, 0.0034388897, 0.00029023932, 0.048117902, -0.0832769, 0.008968996, 0.011544844, -0.06160791, -0.062192123, -0.038690828, 0.040470023, -0.008192259, -0.02656841, 0.020035848, -0.00862378, -0.18025625, 0.06675961, -0.02570537, -0.002253867, -0.038239393, -0.05276505, -0.020341232, -0.0063665933, 0.004550886, -0.01205603, 0.0068910574, 0.01707495, 0.010602137, -0.011372236, -0.0005452101, 0.036539864, -0.0073424946, -0.078762524, -0.028998205, 0.019810129, 0.016663346, 0.0034886806, 0.031281948, 0.015309035, 0.05220739, 0.0287061, -0.017340502, 0.052127726, 0.051490404, -0.025134433, 0.019411802, -0.0053342623, -0.008942441, -0.13744937, 0.066494055, 0.04987054, 0.040974572, 0.042222664, -0.06845913, 0.06580362, 0.02220009, -0.034229565, -0.008856137, 0.02504149, 0.053508595, 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0.006532563, -0.015415255, -0.05146385, -0.054384913, 0.045542054, 0.035982206, -0.0055533424, 0.04933944, 0.06867158, -0.008099316, 0.031839605, -0.0025476331, -0.0136891715, 0.014419437, 0.040177915, -0.0014680009, 0.012115779, 0.0072761066, -0.09958175, -0.041665003, -0.056881096, -0.24791873, 0.005068711, -0.0035683461, -0.024643164, -0.03202549, -0.012839407, 0.030697735, 0.0072030798, 0.016225187, 0.027325232, 0.029210648, -0.0006775708, 0.100112855, 0.062563896, 0.0022704639, -0.042594433, 0.06612228, -0.029130982, -0.037416182, 0.03579632, 0.017539665, -0.029555863, 0.13840535, 0.0053176656, 0.066865824, 0.045117173, -0.01484432, -0.0040828516, 0.001571732, 0.027856335, 0.020341232, 0.015561308, 0.017035117, 0.010011286, 0.012972183, 0.07106154, 0.018920533, -0.0069043348, -0.035052776, 0.03890327, -0.0062006237, 0.014313217, -0.04841001, -0.031149171, 0.107601404, 0.011750647, -0.034681004, -0.054438025, 0.0036413728, -0.08258647, -0.07159264, -0.0053541786, -0.0037177186, 0.015401977, -0.051596623, 0.00088378805, 0.03709752, -0.019199362, -0.06670649, -0.024244837, 0.03967337, -0.0040928097, -0.0025127796, 0.116417706, 0.025214098 ]

Arginine-modulated receptor-activated calcium influx via a NO/cyclic GMP pathway in human SK-N-SH neuroblastoma cells.

The effects of arginine on calcium mobilization in human SK-N-SH neuroblastoma cells were examined. It was found that arginine potentiated an increase in carbachol-induced Ca2+ from the external Ca2+ influx as opposed to an internal Ca2+ release from intracellular pools. The potentiation effect of arginine on carbachol-induced calcium mobilization was mimicked by either 8-bromo cyclic GMP or sodium nitroprusside. In addition; it was found that arginine induced NO production and an increase in cyclic GMP. Mo

8978749

[ -0.068231, -0.06849629, 0.017230185, -0.0024024767, -0.031621832, -0.035388865, 0.045098253, -0.010405758, -0.023835752, -0.039951745, 0.13126244, -0.035574563, -0.006774686, -0.040429257, -0.04480644, 0.025308078, -0.009881822, -0.022443013, -0.081495196, -0.033505347, 0.043029036, 0.009032914, 0.023437826, -0.013808023, 0.050297815, 0.0385988, -0.00484143, -0.003740502, 0.007839138, -0.20002401, 0.06833711, 0.03743155, -0.054224014, -0.05788493, -0.036343884, -0.06085611, 0.033346176, 0.025241757, -0.004314178, 0.00959001, 0.009497161, 0.0034984306, -0.02148799, -0.0015842419, -0.0073549943, 0.023596996, -0.030215828, 0.009775709, 0.0075804857, 0.0025400927, -0.021050273, -0.02445917, -0.020639082, 0.12012052, -0.02069214, 0.027098743, 0.08319301, 0.023676582, 0.040641483, 0.017389355, 0.069716595, 0.032736026, -0.13879651, 0.05809716, 0.09078013, 0.01673941, 0.0028202988, -0.04133122, 0.033346176, 0.006081632, -0.01717713, 0.043267794, 0.019511625, 0.06446397, 0.0016978165, -0.022045087, -0.020148307, -0.0064696097, 0.03973952, 0.009987936, 0.0016671431, 0.016314955, 0.0100807855, -0.033346176, -0.040137444, -0.00065284694, -0.0627131, -0.052632313, -0.06743515, -0.025480513, 0.018331112, -0.041092467, 0.033080895, -0.022443013, -0.08616419, -0.004105267, 0.045920633, 0.0012095285, 0.06870852, 0.32895195, 0.0016696302, 0.011878083, -0.02002893, 0.053109825, -0.046026744, -0.048732642, -0.02116965, -0.049395848, 0.0149354795, 0.096457206, 0.03727238, -0.03268297, 0.010160371, -0.024286736, -0.07221026, -0.009987936, 0.07560589, 0.077091485, -0.08940065, 0.06759432, 0.0026810248, 0.008084524, 0.00067481573, 0.0066221477, 0.08144214, 0.06913297, 0.020798253, 0.056876853, 0.081070736, -0.035972487, 0.012826473, 0.0049243313, -0.0064132367, 0.025798853, -0.01452429, -0.009848663, 0.028438427, -0.09215961, -0.07173275, -0.07507533, 0.019405512, -0.081495196, 0.014802838, 0.0106047215, -0.029022051, 0.098791696, -0.05788493, 0.03560109, 0.022907259, 0.035654146, -0.0066121994, 0.08202576, 0.00059854664, 0.044408515, 0.008767631, 0.0862703, -0.026926309, 0.03958035, -0.00039046464, -0.010750627, -0.014006986, 0.0047187363, -0.009013019, 0.09046179, 0.044700325, -0.053295523, 0.0047419486, -0.019246342, 0.03809476, -0.061174452, 0.011274563, -0.012760152, 0.023053166, -0.0085951965, -0.039102837, -0.011990829, -0.046981767, -0.0643048, 0.003117085, 0.011911244, 0.028836353, -0.05040393, -0.025414191, 0.0066652563, 0.0016016512, 0.0020609237, -0.044594213, -0.007613646, 0.09258406, 0.022827674, 0.015386462, 0.01933919, -0.036900982, 0.013900873, -0.015373198, -0.07618952, -0.018344376, 0.005534484, -0.024724454, -0.02724465, 0.0889762, -0.010777156, 0.02066561, 0.019883024, -0.025865173, 0.0134565225, 0.03231157, -0.024883624, 0.008024836, -0.005328889, -0.044594213, 0.003382369, -0.017455677, -0.0077993446, -0.044832967, 0.0027307654, -0.027138537, 0.030560698, -0.008057997, -0.0055212197, 0.021872653, -0.01673941, 0.011175081, -0.32025063, -0.05624017, -0.041755676, -0.044249345, -0.028809825, 0.021620633, -0.034539957, 0.01300554, 0.05218133, -0.030003602, 0.030534169, 0.058468558, -0.03676834, -0.019034116, -0.065684274, 0.029101636, -0.028995523, 0.0029247543, 0.025533568, -0.047034822, -0.053056765, 0.04021703, -0.04597369, 0.052473143, 0.04544312, -0.030560698, 0.12043886, 0.012269378, -0.003813455, -0.019100437, 0.036370415, -0.02968526, 0.007971779, 0.022389956, 0.023185806, -0.06027249, -0.04098635, -0.034566484, 0.021063536, 0.027669104, -0.026859988, 0.03793559, -0.040959824, -0.030136244, 0.0090196505, -0.05730131, -0.00206424, 0.03247074, 0.05199563, 0.06202336, 0.046318557, -0.008542139, -0.0050006, 0.031064738, 0.05724825, -0.0071626636, -0.013284088, -0.0010304619, -0.08796812, -0.004151692, -0.00860846, 0.05873384, 0.034062445, -0.024313264, 0.027616046, 0.01730977, -0.021912444, 0.046557315, 0.036715284, -0.042286243, 0.021050273, 0.06711681, 0.018198472, 0.008343177, 0.032338098, -0.01870251, 0.014272271, 0.0052294075, -0.035017464, -0.074916154, 0.057672706, -0.056187116, 0.013284088, 0.0075274287, 0.033054367, 0.013688646, 0.053773034, -0.004854694, -0.0053554173, -0.014802838, -0.02525502, -0.019922815, 0.019564683, -0.027191592, -0.06218253, 0.015121179, -0.29117554, -0.0042611216, 0.03331965, -0.002836879, -0.04838777, 0.07427947, 0.064676195, 0.029473035, 0.04101288, 0.003251385, 0.0027456877, -0.018423961, 0.018901473, 0.002410767, -0.013211135, -0.005388578, 0.09475938, -0.024830567, -0.025904967, -0.041782204, 0.028305786, -0.051889516, 0.16914497, -0.026528383, 0.029287335, -0.01370191, -0.05491375, -0.021395141, -0.011301091, 0.02585191, 0.01797298, 0.046875652, 0.04149039, -0.0027324236, 0.009105868, -0.019564683, -0.0251887, 0.013423362, -0.05629323, 0.0027224754, 0.0015021698, 0.02445917, -0.09767751, -0.03204629, 0.09507772, -0.040959824, -0.08011572, -0.01959121, 0.04515131, 0.030825982, -0.018304585, 0.045575764, -0.0073549943, -0.0049840203, 0.035494976, -0.0019896287, 0.0200024, -0.019670796, 0.024154093, 0.0041085836, 0.07343057, -0.042737227, -0.06260698, 0.06536594, 0.020930894 ]

Arginine-modulated receptor-activated calcium influx via a NO/cyclic GMP pathway in human SK-N-SH neuroblastoma cells.

reover; arginine-induced potentiation; NO production; and cyclic GMP increases were all suppressed after the preincubation of cells with N-methyl-L-arginine or N-nitro-L-arginine; nitric oxide synthase inhibitor. It is suggested that the NO production and subsequent cyclic GMP elevation induced by arginine are responsible for the potentiation of carbachol-induced Ca2+ increase. Our results show the existence of a NO/cyclic GMP pathway and an interconnection of NO and Ca2+ signaling pathways in human SK-N-SH

8978749

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Arginine-modulated receptor-activated calcium influx via a NO/cyclic GMP pathway in human SK-N-SH neuroblastoma cells.

neuroblastoma cells. We also observed that NO; which is produced by endothelial CPAE cells; has a modulating effect on cyclic GMP elevation in human SK-N-SH neuroblastoma cells. The intercellular communication role of NO and its cell-diffusing character may also affect the regulation of nonneuronal cells in their interactions with neuronal cells.

8978749

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Expression of microtubule-associated protein-2a and other novel microtubule-associated protein-2 transcripts in human fetal spinal cord.

In human fetal spinal cord (HFSC); six additional microtubule-associated protein-2 (MAP-2) transcripts are generated by alternative splicing of two recently described exons; exon 8 and exon 13. The following three translated proteins are detected by western blot analysis: MAP-2b expressing exon 8 (MAP-2b + 8; MAP-2a); MAP-2b expressing exon 13 (MAP-2b + 13); and MAP-2c expressing exon 8 and exon 13 (MAP-2c + 8 + 13). The finding that MAP-2b + 8 is expressed in HFSC demonstrates for the first time the presen

8978750

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-0.010535564, -0.022629019, -0.014958389, -0.038102303, -0.11523108, -0.0020942404, 0.03348144, -0.066751644, 0.000041953917, 0.03572586, 0.034352805, -0.037627015, 0.003143836, -0.019394416, -0.0034854498, 0.021031521, 0.00075089, -0.04232709, -0.017308427, -0.052598607, -0.03250446, 0.0027956213, -0.32784352, 0.04113887, -0.017136795, 0.0037627015, -0.031580288, 0.027170666, 0.085657574, -0.023355154, -0.04098044, 0.020635447, 0.05045981, 0.039818626, 0.122624464, 0.029784754, 0.002970554, 0.03094657, 0.06395272, -0.024424555, 0.0053337943, -0.076046176, 0.008627809, -0.0041818796, 0.15557781, -0.020886295, 0.021704847, -0.01378337, -0.04383217, -0.032266814, -0.03926412, -0.000028725668, -0.0012096756, 0.098384745, -0.012007639, -0.010383736, 0.013209063, 0.0788451, -0.028306078, -0.03670284, 0.0011164332, 0.00203813, -0.020477017, 0.009043686, -0.057879593, -0.045865353, 0.06257967, -0.045997377, -0.019368012, -0.04087482, 0.04156135, -0.000986884, 0.034062352, 0.0343264, 0.004591156, -0.05492224, -0.0071425317, 0.019315202, -0.04705357, -0.05476381, 0.0025612775, -0.028411698, 0.04269676, -0.108365804, -0.044756345, 0.05856612, -0.00917571 ]

Expression of microtubule-associated protein-2a and other novel microtubule-associated protein-2 transcripts in human fetal spinal cord.

ce of MAP-2a in human fetal CNS. Immunocytochemical studies show that exon 8-specific antibody and exon 13-specific antibody stain independent and overlapping populations of neurons in the lumbar region of the HFSC. Antibody 13-immunopositive neurons have predominantly cytosolic staining; whereas in the antibody 8-immunoreactive neurons staining was observed in the cytosol; dendrites; and some synapses. The prenatal expression of MAP-2a; which has been used as a marker of synaptogenesis; not only demonstrat

8978750

[ 0.03930382, -0.020155126, 0.024194095, 0.033159286, 0.046931513, -0.026643964, 0.028895194, 0.062398784, -0.01740068, 0.0205524, 0.003820469, -0.063193336, 0.015374573, -0.009574347, -0.016553158, -0.001892026, -0.03474839, -0.0074091936, -0.05996216, 0.04099886, 0.055936433, -0.042270146, -0.03469542, -0.08162694, 0.04690503, -0.03212637, 0.022035565, -0.04091941, -0.03506621, -0.16865683, 0.009369087, 0.024644341, 0.0071244794, 0.021969352, -0.0077534993, -0.028100641, 0.006515323, -0.05927355, 0.0055155125, 0.037237983, 0.017956866, -0.00586975, -0.024723798, 0.019691637, -0.0010205022, 0.045289442, -0.025584562, 0.018923571, 0.112932265, -0.018724933, -0.044044644, 0.034880817, -0.05246689, 0.06027998, -0.05042754, -0.040230796, 0.025915625, 0.010375519, -0.016804766, -0.019982973, -0.042693906, -0.0016031733, -0.12426787, 0.04785849, 0.023876276, 0.05519485, 0.00655174, -0.06149829, 0.046083994, 0.00065384974, -0.016844494, 0.057048805, -0.046401814, 0.015692394, 0.03013999, -0.04070753, 0.026511539, -0.042429056, 0.057843357, 0.05257283, -0.06796065, -0.01630155, -0.034271657, 0.017215285, -0.051645853, 0.00078793033, -0.03202043, -0.011388573, 0.006545119, 0.05477109, -0.00560821, -0.0012977676, -0.024273552, 0.015308361, -0.06589481, -0.01357359, 0.031119937, 0.0026816116, 0.05326144, 0.3517215, -0.017771471, 0.00461171, -0.018009836, -0.026127504, 0.019678395, 0.057843357, -0.024644341, 0.019545969, 0.00076516974, 0.024405977, 0.0446538, 0.0063067535, 0.07299281, -0.056995835, -0.0037012862, -0.03705259, -0.034324627, 0.023598183, -0.043938704, 0.0155864535, 0.0075283763, -0.027279604, 0.017016647, -0.04497162, 0.04775255, 0.053314414, 0.022181232, 0.06764282, 0.008309686, -0.0423496, -0.012388384, -0.009355845, -0.019373817, 0.020870222, -0.006545119, -0.003999243, 0.029292468, -0.029742714, -0.041422624, -0.082580395, -0.0049990537, -0.09910707, -0.011150207, -0.06970866, -0.03842981, 0.08978433, -0.0033619464, 0.020936435, -0.068755195, -0.027385546, 0.050718877, 0.092644714, -0.044839196, -0.0060716984, 0.032258794, 0.03223231, -0.06038592, -0.00901154, -0.014818387, -0.015136208, 0.038880058, -0.00823023, -0.04009837, 0.025134316, 0.04822928, -0.076541804, -0.043885734, 0.025174042, 0.03747635, -0.010574157, 0.041237228, 0.019003026, -0.020764282, -0.03527809, -0.04920923, 0.0048964242, -0.007614453, 0.0070251604, -0.010415248, 0.06531214, 0.040416192, -0.05445327, -0.019625425, 0.05890276, 0.03127885, -0.052917138, 0.0067702415, 0.011044268, 0.038880058, 0.037343927, 0.05005675, 0.026405599, -0.045739688, -0.0047772415, 0.070979945, -0.0020774214, 0.069761634, -0.008395762, -0.014195989, -0.033079833, 0.022936055, 0.009183692, 0.019042753, 0.047037456, 0.002666714, -0.022075292, 0.0033784995, -0.05177828, 0.039224364, 0.012295686, -0.00045065975, 0.038059022, -0.041369654, 0.032364734, -0.0754824, 0.057843357, -0.0052903895, -0.046958, 0.039171394, 0.0033271848, 0.057313655, -0.034377597, -0.040018916, -0.34155124, -0.02939841, 0.015427544, 0.019426787, 0.024816494, -0.04497162, -0.08559969, -0.018155504, 0.06785471, 0.03842981, 0.078289814, 0.1052516, 0.003285802, -0.015838062, 0.028365493, 0.08141506, 0.046507753, -0.08999621, 0.005932652, -0.02101589, -0.06022701, 0.03594022, 0.015692394, 0.016632613, 0.09624668, -0.010203367, 0.12532727, 0.024498675, 0.041634504, 0.022141505, -0.045289442, -0.023492243, 0.03612561, -0.04444192, 0.0515664, 0.016235339, -0.03249716, -0.020419976, -0.0021469446, 0.0026137438, -0.043938704, -0.013136586, 0.0077932267, -0.05445327, 0.0042905784, 0.00078048144, 0.005753878, 0.0146329915, 0.046958, 0.02652478, 0.014169504, -0.042799845, 0.018513052, 0.071827464, -0.020287551, -0.019956488, -0.030828603, -0.055830494, -0.036575858, 0.058478996, 0.008826144, 0.01021661, -0.0013780504, -0.04070753, 0.017374195, -0.036602344, -0.06425274, 0.009680287, 0.023068482, -0.06965569, 0.027001511, 0.093757086, 0.040283766, -0.018195232, 0.05466515, 0.02049943, -0.015017025, -0.07384033, -0.00327587, -0.027915247, 0.058055237, -0.061816115, 0.01362656, 0.043700337, 0.09889519, 0.041687474, -0.011600453, 0.012143397, 0.043938704, 0.032470677, 0.00069357734, 0.008660613, -0.0017529795, -0.01766553, -0.0106205065, -0.0064855274, -0.28349602, 0.0223269, 0.0055320654, 0.0028438326, -0.05561861, 0.012911463, 0.018301172, -0.088830866, -0.023929246, 0.0060518347, 0.05535376, 0.041078318, 0.105622396, -0.008594399, -0.04086644, 0.035384033, 0.062080964, 0.010938327, 0.0011669977, -0.057949297, -0.012818766, -0.054161932, 0.11950056, 0.015175936, 0.026643964, -0.03609913, -0.02206205, -0.021903139, -0.07214528, -0.0056346953, 0.03390087, 0.024564886, -0.018830873, -0.0035291333, -0.016102912, 0.044945136, 0.029901626, -0.007832955, -0.0074555427, -0.0108456295, -0.06992054, 0.001996311, -0.06457056, -0.10477487, 0.06149829, -0.053552777, -0.028921679, -0.025531592, 0.036575858, 0.02725312, 0.028974649, -0.007925652, 0.0129776765, -0.031172907, 0.012289065, -0.04931517, -0.0030010876, -0.0066742334, -0.036867194, 0.0029150113, 0.0526258, -0.03850927, -0.04552781, 0.11812334, 0.05214907 ]

Expression of microtubule-associated protein-2a and other novel microtubule-associated protein-2 transcripts in human fetal spinal cord.

es the presence of a mature MAP-2 isoform in HFSC; but suggests that MAP-2a is important during human fetal as well as postnatal synaptogenesis.

8978750

[ -0.034312993, -0.0094465185, 0.028019665, -0.06575351, 0.03799498, 0.040945794, 0.07881021, 0.0050300914, 0.046821304, 0.008036396, -0.0047722217, -0.098238565, 0.043139316, 0.027993552, 0.022953669, 0.020525124, -0.05415917, -0.022000529, -0.068782665, 0.0146104405, 0.06664137, -0.06355999, 0.022888385, -0.025055796, 0.04118081, 0.040763, -0.012939184, -0.014897688, -0.039483443, -0.07546769, -0.01730012, 0.0068417075, 0.07149845, -0.024703266, -0.007840545, 0.021295467, -0.013670359, 0.014767121, 0.06544015, -0.063664444, -0.027105696, -0.044314418, -0.004847298, -0.05447253, 0.02108656, -0.03969235, -0.045202274, 0.026635656, 0.02069486, -0.028306913, -0.052122325, -0.036323722, 0.035174735, 0.04663851, 0.040789112, 0.09865638, 0.054054715, -0.004530673, 0.030474324, 0.058755122, 0.04838811, 0.011463777, -0.15218882, 0.0319889, 0.01630781, 0.0075598257, 0.027732419, -0.061314236, -0.02089071, 0.052200664, 0.0023028743, 0.0063553457, -0.029482014, 0.014923802, -0.016007507, 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0.048153087, 0.0067241974, 0.08168268, -0.015367729, -0.09212803, 0.023032008, -0.02381541, -0.024324622, 0.03914397, -0.021204071, -0.0207732, 0.032693963, -0.07165514, 0.002895322, -0.0067568393, -0.02002897, -0.09656731, 0.031257726, 0.056352694, -0.002084175, -0.031336065, -0.001390538, 0.048753697, -0.07698227, -0.03428688, 0.11646571, -0.011124304, 0.030892137, 0.0075924676, 0.023280086, 0.0051084314, -0.044497214, -0.03415631, 0.08163045, -0.007612053, 0.004909317, 0.0062508923, 0.015446069, 0.008173491, 0.018122692, -0.031571086, -0.02373707, 0.053375766, 0.044314418, 0.044027172, -0.03684599, -0.0013317828, 0.04146806, 0.024833832, 0.019833118, -0.025839198, 0.09494828, -0.03977069, 0.015785543, 0.016138073, -0.046742965, -0.026870677, 0.033477362, -0.041807536, 0.025369156, 0.043974947, -0.0083367, -0.023240916, 0.036898218, 0.016973702, -0.041050248, -0.009237611, 0.031101046, 0.042643163, 0.00012312054, 0.039274536, -0.03397352, -0.04415774, -0.059329618, -0.30249748, 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-0.008447682, -0.037054896, -0.06737254, 0.01777016, 0.06951384, 0.03392129, 0.047604706, 0.09171022, 0.06408226, 0.008558663, 0.07014056, -0.008121264, 0.06570128, -0.031962786, -0.0207732, 0.0021315054, -0.007768733, -0.0639778, -0.06079197, -0.031179385, -0.30584002, -0.0013831935, -0.02057735, 0.051443376, 0.0046775606, -0.019519757, -0.061993185, 0.059068482, -0.08507742, 0.045881223, -0.021700226, 0.058389537, 0.004347879, -0.028959747, 0.0070245015, -0.018422995, 0.012142725, 0.0594863, 0.0029442846, -0.05018993, 0.121270575, 0.0062737414, 0.17809331, 0.026452862, -0.025565008, 0.014793235, -0.045672316, 0.042590935, 0.06972275, -0.033164002, 0.021713283, 0.041102473, 0.05233123, 0.009583614, 0.05180896, 0.071237326, -0.054054715, 0.02211804, 0.026648713, -0.026792336, -0.017561253, 0.026687883, -0.058076177, 0.03483526, 0.09964869, -0.014571271, -0.04676908, -0.029952057, -0.03768162, -0.0063129114, -0.044262193, 0.024677152, -0.02361956, 0.019297794, 0.022013586, -0.013513679, 0.022444457, -0.0403713, -0.052070096, -0.016764795, -0.04324377, -0.04507171, -0.0046220697, -0.008800212, 0.029038088 ]

Brain-derived neurotrophic factor increases the stimulation-evoked release of glutamate and the levels of exocytosis-associated proteins in cultured cortical neurons from embryonic rats.

Differentiation and survival of neurons induced by neurotrophins have been widely investigated; but little has been reported about the long-term effect of brain-derived neurotrophic factor (BDNF) on synaptic transmission. Among many steps of neurotransmission; one important step is regulated release of transmitters. Therefore; the release of glutamate and GABA from cortical neurons cultured for several days with or without BDNF was measured by an HPLC-fluorescence method. Although BDNF had little effect on

8978748

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Brain-derived neurotrophic factor increases the stimulation-evoked release of glutamate and the levels of exocytosis-associated proteins in cultured cortical neurons from embryonic rats.

the basal release of glutamate; high K(+)-evoked release was greatly increased by BDNF. BDNF also tended to increase evoked release of GABA. Recently; several proteins involved in the step of "regulated release" have been identified. Thus; the effect of BDNF on the levels of these proteins was then investigated. Neurons were cultivated with or without BDNF; collected; and electrophoresed for western blotting. BDNF increased levels of synaptotagmin; synaptobrevin; synaptophysin; and rab3A; which were known a

8978748

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Brain-derived neurotrophic factor increases the stimulation-evoked release of glutamate and the levels of exocytosis-associated proteins in cultured cortical neurons from embryonic rats.

s vesicle protein. Levels of syntaxin; SNAP-25; and beta-SNAP were also increased by BDNF. In addition; the numbers of cored and clear vesicles in nerve terminals or varicosities were also increased by BDNF. These results raise the possibility that BDNF increases regulated release of neurotransmitters through the up-regulation of secretory mechanisms.

8978748

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-0.044184517, -0.035205, 0.031269856, -0.10120446, 0.014248384, 0.01653288, 0.0011810379, 0.03243191, -0.048410174, 0.12254403, -0.036657568 ]

Activation of protein kinase C-alpha and translocation of the myristoylated alanine-rich C-kinase substrate correlate with phorbol ester-enhanced noradrenaline release from SH-SY5Y human neuroblastoma cells.

The aim of this study was to investigate the mechanism by which short-term pretreatment with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 100 nM) enhances noradrenaline (NA) release from the human neuroblastoma cell line SH-SY5Y. Subcellular fractionation and immunocytochemical studies demonstrated that an 8-min TPA treatment caused translocation of the alpha-subtype of protein kinase C (PKC) from the cytosol to the plasma membrane. In contrast; TPA altered the distribution of PKC-epsilon fr

8978751

[ -0.02444296, 0.007087796, -0.0076574693, 0.045573864, -0.0044977693, -0.001712332, 0.05222447, 0.017964581, -0.04962782, -0.06942065, 0.0016974277, -0.08160901, 0.036538582, -0.0118902745, -0.014679024, 0.013294585, -0.012281097, 0.0027026362, -0.035266753, 0.041493412, -0.03166324, -0.009015411, 0.008829936, -0.036538582, 0.005865648, -0.02420449, -0.019183418, -0.038870268, -0.02502588, -0.17413455, 0.005941825, 0.030152941, -0.0053986483, 0.007882689, -0.0027274766, -0.034869306, -0.03023243, -0.025529314, -0.0110092675, 0.04106947, 0.022773685, 0.028987097, -0.0053721517, -0.0028566467, 0.059034053, 0.006677101, -0.009551964, 0.021634337, 0.08478858, 0.035558213, 0.056543387, -0.033835944, 0.009644701, 0.04345415, -0.050820157, 0.05156206, 0.03675055, 0.009141269, 0.0245092, 0.02763578, 0.010896658, 0.065234214, -0.11732621, 0.0750379, 0.060305882, -0.016003845, -0.0100024035, -0.08431165, 0.04263276, 0.0913597, -0.13343604, 0.008213894, 0.014122599, 0.07191132, 0.047852557, 0.03431288, -0.014215336, -0.0018001014, 0.018746227, -0.017355163, -0.030126445, -0.014970484, -0.0030802104, -0.065181226, 0.01255931, 0.0021230266, 0.03900275, -0.044778973, 0.023356605, 0.0057132933, -0.020600976, -0.044010576, 0.0839407, 0.014361067, -0.047826063, -0.020309515, 0.038870268, 0.013897379, -0.013672159, 0.38197258, -0.03097433, -0.026244717, -0.07196431, 0.002022009, -0.0057199174, -0.03794289, -0.023157882, 0.018004326, -0.03208718, -0.020468494, 0.025953256, -0.017394908, 0.03757194, -0.008167526, -0.003742621, 0.07016256, 0.010413098, -0.007220278, -0.03810187, 0.05622543, 0.013195223, -0.043878093, 0.0047428613, -0.004792542, 0.02578103, -0.0029129516, -0.013321081, 0.09422132, 0.03979764, 0.013360826, 0.059087045, 0.045865323, 0.015261945, 0.020534735, -0.058610108, 0.055748496, -0.009783808, -0.012731536, -0.01901119, 0.026761398, 0.03587617, -0.0869083, -0.043533638, -0.08197996, -0.04016859, 0.0005431769, -0.034657333, 0.055748496, -0.04016859, 0.011598813, 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-0.023303613, -0.06745992, -0.031451266, 0.011678303, 0.09967958, 0.031239294, 0.010737679, 0.031106813, -0.028404176, 0.035823178, 0.03675055, -0.02792724, 0.031901706, 0.005445017, -0.00027303747, -0.04276524, 0.0008818344, 0.011095381, 0.009883169, -0.0056934212, -0.29676005, -0.040751513, 0.018706482, -0.015725633, -0.056172438, 0.009273752, 0.045043934, -0.044540502, -0.057444267, 0.010207751, 0.04204984, 0.02309164, 0.071116425, -0.030099947, 0.0029543522, -0.0046070674, 0.037757415, -0.033888936, -0.015288441, 0.029940968, 0.007948929, -0.04194385, 0.14880396, 0.00623991, 0.014029861, 0.014241832, -0.079012364, -0.0075448593, -0.011923395, -0.036989022, 0.0020750018, 0.029967466, -0.016149575, -0.02250872, 0.011227864, -0.0024177996, -0.022574961, -0.004090387, -0.0015591495, 0.01285077, -0.047031168, 0.0683608, -0.037042014, -0.017580383, 0.031239294, -0.026125483, -0.03423339, 0.0026496432, -0.03990363, -0.01080392, -0.034895804, 0.015937604, 0.004842223, 0.014586287, -0.02949053, -0.04250028, 0.00006882862, -0.0074256253, 0.055059586, 0.0008694142, 0.039691657, 0.05354929, -0.09252554, 0.112026915, 0.012208232 ]

Activation of protein kinase C-alpha and translocation of the myristoylated alanine-rich C-kinase substrate correlate with phorbol ester-enhanced noradrenaline release from SH-SY5Y human neuroblastoma cells.

om cytosolic and membrane-associated to cytoskeleton- and membrane-associated. TPA had no effect on the cytosolic location of PKC-zeta. Subcellular fractionation studies also showed that the myristoylated alanine-rich C-kinase substrate (MARCKS); a major neuronal PKC substrate that has been implicated in the mechanism of neurotransmitter release; translocated from membranes to cytosol in response to an 8-min TPA treatment. Under these conditions the level of phosphorylation of MARCKS increased threefold. Th

8978751

[ -0.026700297, 0.042947486, 0.04841161, 0.0009626559, 0.0133831445, -0.04484805, -0.005051675, -0.00274856, -0.013752698, 0.01874168, 0.03669146, -0.09787909, 0.04590392, -0.04645825, -0.010340921, 0.0016910408, -0.05680577, 0.024509368, -0.041733235, 0.017949779, -0.0076154578, -0.06287702, 0.021684917, -0.036585875, 0.07095442, 0.046590235, -0.011858732, -0.019137632, -0.009925172, -0.19660288, -0.01736905, 0.00017116632, -0.003451373, -0.06736446, -0.039463118, -0.049335495, 0.037694536, -0.03748336, -0.032784745, 0.022846373, 0.091438286, 0.014293832, 0.010921649, 0.0363747, 0.03281114, 0.009337844, -0.09175505, 0.015851239, -0.0061207428, -0.02173771, -0.014082657, 0.030461831, 0.053374197, 0.03328628, -0.074808344, 0.093233265, 0.064513616, 0.0012546697, -0.008011409, -0.006642078, -0.03743057, 0.050206587, -0.12153056, 0.025261674, 0.09106873, 0.03484369, -0.04986343, -0.05355897, -0.032679155, -0.0011895028, -0.036480285, 0.03362944, -0.027109446, 0.0045765336, 0.00953582, 0.035028465, 0.022450423, -0.027901348, 0.023572283, -0.0037846318, -0.05828399, -0.023413904, -0.031068956, -0.027505396, -0.002232174, -0.047250155, -0.039014373, -0.056119457, -0.025631228, 0.06995135, 0.016062412, -0.010974443, 0.07428041, -0.004220178, -0.07855668, 0.011522175, 0.08388882, 0.021803703, 0.06319378, 0.36575314, -0.013620715, -0.008559141, -0.053136624, 0.044320118, 0.04146927, 0.0011144371, -0.017910184, 0.026330743, -0.010387115, -0.008037806, 0.07438599, -0.054166097, 0.04915072, -0.033391867, -0.02684548, -0.050734524, -0.0026083272, 0.02222605, -0.038196076, 0.023466697, -0.058231194, -0.021130586, -0.031966444, -0.025763212, 0.047857277, 0.03967429, -0.02367787, 0.051051285, -0.040255018, -0.013059784, 0.044214528, -0.018622896, 0.02642313, -0.00468542, -0.007740842, 0.006091046, 0.018966053, -0.027083049, -0.0094500305, -0.03489648, -0.028006935, -0.06609742, 0.007120519, 0.00056588, -0.027452603, 0.046167888, -0.070532076, 0.05648901, 0.0071403165, 0.038460042, -0.01608881, 0.05891751, -0.055010792, -0.015494883, 0.010057156, 0.060870867, -0.009430233, -0.0076418547, -0.012017113, 0.0061240424, 0.02126257, -0.044663273, -0.012888205, 0.09011845, 0.026805883, -0.09529221, -0.035582796, 0.029722722, -0.00069002714, -0.029141994, 0.017606622, -0.025235279, -0.01648476, -0.05479962, 0.013178569, -0.088957, -0.05802002, 0.007866227, 0.053136624, 0.042604327, 0.014531402, -0.06979296, -0.011581567, 0.02610637, -0.0031544098, -0.025750015, -0.08019328, 0.09259974, 0.023466697, -0.0016943404, 0.016339578, -0.04065097, -0.020893015, -0.0018857167, 0.05749209, -0.036480285, -0.032441586, -0.028191712, 0.016154801, -0.0021942286, 0.07417482, -0.02787495, 0.034394946, 0.015626866, -0.019216822, 0.0014353225, 0.034790896, -0.043765783, 0.015178122, 0.032362398, 0.0070347297, -0.015059337, -0.016682737, 0.012683631, -0.066203006, 0.08204105, 0.017567027, -0.0331279, 0.06044852, 0.052476708, 0.013567922, 0.021288967, -0.00028170264, -0.32119545, -0.07728964, -0.020299088, 0.009687602, 0.03822247, -0.0525295, 0.022582406, 0.02966993, -0.007259102, -0.019612774, 0.06894827, 0.07084884, 0.0037813322, 0.019929534, -0.05205436, 0.07934858, 0.014993345, -0.054588445, -0.037509758, 0.0056785974, -0.032995917, 0.013897881, 0.0045600357, 0.042208377, 0.054746825, -0.0030125272, 0.13388424, 0.036585875, 0.024601756, 0.036110733, -0.01851731, 0.035899557, -0.017844193, -0.022846373, -0.0029679828, 0.0018890162, 0.0069951345, -0.03832806, 0.005959063, 0.028086126, -0.021275768, 0.0032847435, -0.031095352, -0.0169731, 0.023453498, 0.002334461, -0.027017057, 0.014848163, -0.007826632, 0.012571445, 0.023875846, 0.009872379, 0.009192662, 0.042789105, -0.019955931, 0.019388402, -0.068209164, 0.03378782, -0.030250657, -0.00066651753, 0.031913653, -0.028191712, 0.035028465, -0.030989766, -0.022569207, -0.030725798, -0.004091494, 0.018213747, 0.070215315, 0.014821766, 0.04645825, 0.08695084, 0.02821811, -0.016603546, -0.018636094, 0.018081762, -0.035266038, -0.07739522, -0.044029754, -0.031649683, 0.04252514, -0.05553873, 0.03766814, 0.07533628, 0.00185932, -0.009826184, 0.037140206, 0.00051597366, 0.04315866, 0.026634304, -0.027637381, -0.011469381, -0.040967733, -0.060184553, 0.010644483, 0.020866618, -0.27283666, -0.001664644, -0.038671214, -0.01842492, -0.03814328, 0.024271797, 0.11783502, -0.062349085, -0.0051275655, 0.019348806, 0.0010451457, 0.053321403, 0.053849336, 0.06578066, -0.04988983, 0.07417482, 0.05303104, -0.053083833, 0.0021282367, 0.0033243387, 0.022991555, -0.04962586, 0.17126201, -0.001446046, 0.03830166, -0.036955427, -0.012386668, 0.04178603, 0.023704268, -0.017250266, 0.037166603, 0.06636139, 0.061451595, -0.046616632, -0.040466193, 0.07686729, -0.016075611, 0.0077342433, 0.06314099, 0.015745651, 0.009463229, 0.02093261, -0.058336783, -0.06335216, 0.07528348, -0.04453129, -0.061082043, 0.057650466, -0.01317197, 0.026251553, -0.058970302, -0.0135085285, -0.0048536994, -0.030356243, -0.040809352, -0.02561803, 0.032256808, 0.011409989, -0.034447737, -0.01244606, 0.02126257, -0.021658521, -0.028350092, 0.06578066, 0.020351881 ]

Activation of protein kinase C-alpha and translocation of the myristoylated alanine-rich C-kinase substrate correlate with phorbol ester-enhanced noradrenaline release from SH-SY5Y human neuroblastoma cells.

e ability of TPA to enhance NA release and to cause the translocation and phosphorylation of MARCKS was inhibited by the PKC inhibitor Ro 31-8220 (10 microM). Selective down-regulation of PKC subtypes by prolonged exposure to phorbol 12;13-dibutyrate (100 nM) attenuated the TPA-induced enhancement of NA release and the translocation of MARCKS over an interval similar to that of down-regulation of PKC-alpha (but not -epsilon or -zeta). Thus; we have demonstrated a strong correlation between the translocation

8978751

[ -0.009175108, 0.0142650455, 0.041301206, 0.0045082304, 0.01156804, -0.016182035, 0.027498882, 0.014503017, -0.0071325228, 0.004633826, 0.019989572, -0.12099509, 0.039952703, 0.021787576, -0.031412184, -0.0005569185, 0.01563999, -0.0059459726, -0.024312714, -0.030328095, 0.044421274, -0.04820237, -0.028424326, -0.060497545, -0.051058024, 0.030380977, 0.0025433162, -0.012804167, -0.016115932, -0.18117534, -0.010675648, -0.01692239, 0.045954864, -0.02357236, -0.025132393, -0.045161627, -0.00899002, -0.039979145, -0.06176672, 0.0013567659, 0.08138612, -0.0030919719, -0.077049755, -0.0036455852, 0.02165537, 0.00018147362, -0.04756778, -0.047911517, -0.0018773276, -0.011244135, -0.022025548, -0.058170713, 0.016803404, -0.024035081, -0.044262625, 0.041962236, 0.06684344, 0.029508417, 0.016446447, -0.0061839437, 0.020954678, 0.050238345, -0.1179279, 0.063987784, 0.017411552, 0.004498315, 0.013332992, -0.050661404, 0.07583346, -0.01028564, -0.072766274, 0.01905091, 0.032707807, 0.02723447, 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-0.0069804857, 0.0063525066, -0.04029644, -0.01647289, 0.028345002, 0.038419113, 0.05637271, 0.0853523, 0.0012154705, -0.053887233, 0.07895353, 0.029270446 ]

Activation of protein kinase C-alpha and translocation of the myristoylated alanine-rich C-kinase substrate correlate with phorbol ester-enhanced noradrenaline release from SH-SY5Y human neuroblastoma cells.

of MARCKS and the enhancement of NA release from SH-SY5Y cells due to the TPA-induced activation of PKC-alpha.

8978751

[ 0.0036890283, 0.0069190073, 0.016672146, -0.027210327, 0.02767603, -0.039119, 0.010784337, -0.023311732, -0.00371564, -0.010232147, 0.059077676, -0.043749414, 0.035553053, 0.039331894, -0.064772554, -0.05167966, 0.026292227, 0.029299334, -0.005365557, 0.009573511, -0.0055884286, 0.03092264, -0.05849222, -0.010910742, 0.010065825, 0.015847187, 0.010484957, -0.034754705, -0.05271751, -0.1705269, 0.025480574, 0.037309416, 0.022287186, -0.050961148, -0.06301619, -0.07525751, 0.07712032, 0.042897843, -0.02082355, 0.01044504, 0.03164115, -0.020331236, -0.050349083, 0.010824255, -0.014889171, 0.04217933, -0.025600327, -0.026970822, -0.052584454, -0.027729252, -0.022060988, -0.050029743, -0.0014220555, 0.011715742, -0.025600327, 0.059343792, 0.025626937, 0.026465202, 0.012826774, 0.005365557, 0.02454917, 0.019266773, -0.122626096, 0.054500487, 0.01249413, -0.0012906609, 0.047049247, -0.09361949, 0.07743966, 0.06237751, -0.031321812, 0.051945776, 0.028155036, 0.053968254, 0.0097331805, 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0.025014872, -0.030044457, 0.0019143695, 0.058758337, 0.02489512, -0.0013388944, -0.05625685, -0.01546132, 0.043430075, 0.026199086, -0.008242932, 0.015341568, 0.0068391724, -0.007584296, 0.014077518, 0.025533797, -0.015062146, -0.015727436, -0.025347516, -0.2876178, 0.038160983, -0.0064366725, 0.037309416, -0.025347516, 0.009407189, 0.03757553, -0.02618578, -0.008229626, 0.012454213, -0.014410163, 0.03943834, 0.04521305, 0.032013714, 0.058918007, 0.09729189, 0.0733947, -0.061898503, 0.0031401648, -0.05742776, 0.043962307, -0.03041702, 0.18234245, 0.009194296, 0.00096217444, 0.03057669, 0.036191728, -0.013199337, -0.012873345, 0.00058379123, 0.0826023, 0.011263345, -0.029618673, -0.003387985, 0.0055851024, 0.025347516, 0.010438386, 0.049444288, 0.021941235, 0.053861808, 0.02568016, 0.0043010945, -0.084518336, 0.021116277, 0.09202279, -0.035606276, -0.05678908, 0.00993942, 0.039518174, -0.016778592, 0.043802638, -0.021728344, 0.026398674, 0.016685452, -0.022952475, -0.03318462, -0.03858677, 0.020384459, 0.060088914, 0.053462636, 0.025773302, -0.029325945, 0.02319198, 0.0768542, 0.019892145 ]

Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A.

This study was undertaken to characterize further the central cannabinoid receptors in rat primary neuronal cell cultures from selected brain structures. By using [3H]SR 141716A; the specific CB1 receptor antagonist; we demonstrate in cortical neurons the presence of a high density of specific binding sites (Bmax = 139 +/- 9 fmol/mg of protein) displaying a high affinity (KD = 0.76 +/- 0.09 nM). The two cannabinoid receptor agonists; CP 55940 and WIN 55212-2; inhibited in a concentration-dependent manner cy

8978752

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0.02059024, -0.07581012, -0.01846386, 0.0067819683, 0.05076901, -0.021461925, -0.0060687717, -0.004147104, -0.02073552, -0.022584548, 0.054467063, 0.020577032, 0.007970628, -0.0024846306, -0.010281913, 0.003353013, -0.057636824, -0.03993899, 0.006861212, 0.0024251975, -0.27978426, -0.0048569986, 0.026612787, 0.000058091653, -0.058587752, -0.0071517737, 0.08336472, -0.015479, -0.030482536, 0.005494253, -0.0005774083, -0.0029452364, 0.07929686, -0.019361958, -0.022492098, 0.013260168, 0.041550286, -0.043795533, -0.012844137, -0.027312776, 0.0059400005, 0.017882736, 0.15722016, -0.013167717, 0.031486295, 0.03740318, 0.032569297, -0.02028647, 0.036452252, -0.011853586, -0.012593197, 0.016390307, 0.021158155, -0.013603559, 0.008505526, 0.01126586, 0.029558023, 0.002996415, 0.0064385775, 0.0054414235, 0.01756576, 0.021078913, -0.044218168, -0.048708662, 0.06804421, -0.054942526, -0.0606481, -0.003972107, 0.010559267, -0.0071517737, 0.004810773, -0.034761716, 0.005629628, -0.029452365, 0.022346817, 0.0053786887, -0.033546638, -0.01016965, -0.015571452, 0.014316754, 0.04897281, 0.06307825, -0.042395554, 0.0946702, 0.040652186 ]

Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A.

clic AMP production induced by either 1 microM forskolin or isoproterenol with EC50 values in the nanomolar range (4.6 and 65 nM with forskolin and 1.0 and 5.1 nM with isoproterenol for CP 55940 and WIN 55212-2; respectively). Moreover; in striatal neurons and cerebellar granule cells; CP 55940 was also able to reduce the cyclic AMP accumulation induced by 1 microM forskolin with a potency similar to that observed in cortical neurons (EC50 values of 3.5 and 1.9 nM in striatum and cerebellum; respectively).

8978752

[ -0.06212339, -0.04066786, -0.014316882, -0.024490446, -0.023157721, -0.006755985, 0.051672727, -0.01012738, -0.0069407187, 0.0031916092, 0.0018011561, -0.05827037, -0.009494006, 0.04190822, 0.006185289, -0.016639251, -0.020030439, 0.02984773, -0.07436861, -0.03974419, 0.048769765, -0.07827442, 0.048400298, -0.019555409, 0.010265931, -0.012166051, -0.06259842, 0.0009319169, 0.015134989, -0.2109134, 0.030190807, 0.022115294, 0.005390273, -0.0034340725, -0.010661788, -0.01838103, -0.0052286307, -0.01813032, -0.014593983, -0.0014687999, 0.037474602, 0.034782767, -0.013775876, 0.015134989, 0.06814044, -0.022168076, -0.012713655, -0.014528006, 0.045312602, 0.00031544972, -0.0060302443, 0.011809778, 0.03781768, 0.025915535, -0.012687265, 0.042066563, -0.0097909, 0.0018819772, -0.010595812, 0.04053591, 0.016071854, 0.041723486, -0.095903315, 0.048189174, 0.06254564, 0.07341856, 0.030269979, -0.048162784, 0.0132744545, 0.016692033, -0.006581147, 0.013459189, 0.028185124, 0.037025962, -0.0028237905, 0.02245837, 0.013921023, -0.007395956, 0.08988627, 0.03641898, 0.009124538, -0.023738313, 0.04441532, -0.012416761, -0.038530227, 0.017905999, -0.06703204, -0.012825815, -0.00920371, 0.032381225, -0.031668678, -0.051461603, 0.030243589, 0.01563641, -0.07025169, 0.03454525, 0.009909658, -0.006716399, -0.05410066, 0.43006065, -0.01443564, -0.056845278, -0.046737693, 0.018315053, 0.058375932, 0.010839925, -0.046500176, 0.0041037328, 0.01933109, 0.061437238, 0.04613071, -0.044072244, -0.03549531, -0.010826729, 0.016573275, -0.026192637, 0.024622397, -0.020439493, -0.052147757, -0.0063007474, -0.014039781, -0.029583825, 0.020874938, -0.03264513, 0.01586073, 0.0054199626, -0.052464444, 0.067454286, 0.046368223, 0.021653458, 0.044547275, 0.099598, -0.061806705, 0.014158539, -0.006647124, -0.044283368, 0.015847534, -0.09769788, -0.041116502, -0.028290687, 0.008623118, -0.050722666, -0.05642303, -0.00013257135, -0.07415749, 0.059378773, 0.0033318088, -0.00945442, -0.015900316, 0.067454286, -0.0048327725, 0.09004461, -0.017325407, 0.048928108, -0.007270601, 0.009329065, 0.0110378545, 0.03261874, 0.010173563, -0.007923767, -0.04343887, -0.030639447, -0.0033779924, 0.06719038, 0.049983732, -0.10218427, -0.04193461, 0.013459189, 0.025585653, -0.04288467, 0.07700767, -0.016401736, -0.03731626, 0.039928924, -0.019119965, -0.06423464, -0.031167258, -0.0015892069, 0.041116502, 0.028105952, 0.023144526, -0.1183353, -0.037844073, 0.04341248, 0.046394616, -0.061490018, -0.016019074, 0.054681253, -0.009190515, -0.010945487, -0.028924061, 0.059853803, -0.050194856, 0.044732008, -0.007976549, 0.00455897, 0.023461213, -0.0021376358, 0.019449847, -0.020888133, 0.069935, 0.014514811, 0.0022613415, 0.084344245, -0.025532873, 0.0003896732, 0.0024988567, 0.031510334, 0.02847542, -0.00023607186, -0.033357676, 0.021402748, -0.03623425, 0.014593983, -0.05505072, 0.024068195, -0.020822156, 0.046948817, 0.0377649, 0.016230198, 0.03974419, 0.04188183, -0.073735245, -0.29684108, -0.024780741, 0.02045269, -0.035284188, 0.017932389, -0.06412908, 0.03541614, 0.038345493, 0.010008622, -0.008715484, 0.019964462, 0.0023339156, -0.08613881, 0.000121231664, -0.053388115, 0.06486801, 0.03602312, -0.034677204, -0.000414002, 0.033357676, 0.020822156, 0.012634483, 0.014646764, 0.045523725, 0.0107475575, -0.03312016, 0.1334307, 0.014567592, 0.02232642, -0.017576117, -0.0293727, 0.0321701, 0.00008932588, -0.057320308, 0.004618349, 0.052121367, -0.04061508, -0.09210307, -0.019792924, -0.019172747, -0.034307737, -0.009078355, -0.045866802, -0.086508274, -0.030956134, 0.022946596, -0.028237905, -0.014039781, 0.0012609742, -0.01913316, 0.050590716, -0.017998366, 0.02615305, 0.028580982, 0.0054727434, -0.009032171, -0.021719435, 0.005871901, -0.045470946, 0.039876144, 0.027446188, -0.033647973, -0.037395433, -0.012172649, -0.0071848314, -0.013987, -0.027208673, -0.007673057, 0.046790473, -0.045550115, -0.024490446, 0.06803488, 0.035178624, 0.059853803, 0.03781768, -0.017114282, 0.0073893582, -0.0034868536, -0.04011366, -0.0012964365, -0.010107587, -0.06486801, 0.07120175, 0.031061696, -0.035759218, 0.038820524, 0.006907731, 0.030454714, 0.005683868, -0.042594373, -0.0108729135, 0.019924877, -0.045365382, -0.08708887, 0.035257798, 0.013254662, -0.28459585, 0.09326426, 0.0016411634, 0.04887533, -0.024094587, 0.063337356, 0.04021922, -0.03306738, 0.013815462, 0.06196505, 0.0016461115, 0.044969525, 0.050537933, 0.06492079, -0.001099332, 0.03868857, 0.10075918, -0.04394029, 0.017299015, 0.0690905, 0.018064342, 0.0020122807, 0.16066577, -0.0034076818, 0.016678838, -0.012594897, -0.06877381, -0.034439687, -0.0060302443, -0.00038142616, -0.0475558, -0.00039338437, 0.01306333, -0.009302675, -0.00011947916, 0.020518664, -0.001768168, 0.0062479666, -0.014277296, 0.0002618439, 0.061331674, -0.01728582, -0.008873828, -0.05225332, 0.079118915, -0.0038035403, -0.03876774, -0.03354241, 0.0052484237, 0.002190417, -0.022286832, -0.041565143, -0.023342455, -0.041776266, -0.011110428, -0.016837182, 0.08365809, -0.022471568, -0.024332102, 0.011651435, -0.0035726228, -0.006620733, -0.048400298, 0.07336577, -0.01603227 ]

Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A.

SR 141716A antagonized the CP 55940- and WIN 55212-2-induced inhibition of cyclic AMP accumulation; suggesting CB1 receptor-specific mediation of these effects on all primary cultures tested. Furthermore; CP 55940 was unable to induce mitogen-activated protein kinase activation in either cortical or striatal neurons. In conclusion; our results show nanomolar efficiencies for CP 55940 and WIN 55212-2 on adenylyl cyclase activity and no effect on any other signal transduction pathway investigated in primary n

8978752

[ -0.030485945, 0.016236216, -0.060918916, -0.014157026, 0.019123241, -0.0021834795, -0.00038177785, 0.025479998, 0.0014228208, 0.006068716, 0.003100574, -0.13825946, -0.007012297, -0.009071621, -0.017825404, 0.019798648, -0.113891885, 0.061077833, -0.042590268, 0.028367026, 0.01846108, -0.036895674, -0.024592701, -0.015242972, 0.042457834, 0.034088105, -0.044550266, 0.006032297, -0.088729724, -0.18116756, 0.009879459, 0.03753135, -0.005115202, -0.019255674, -0.025890538, -0.03263135, 0.01303135, 0.009826486, -0.0011687161, 0.028314052, 0.03623351, 0.023917295, 0.022698918, 0.03443243, 0.04974162, -0.008714054, -0.012912162, 0.036180537, -0.0029681418, 0.0043106754, 0.007336756, -0.020672701, -0.007469189, 0.046695672, 0.031015674, 0.028711349, 0.051198374, 0.034273513, 0.031677835, 0.022844594, -0.029399998, 0.07606918, -0.13762377, 0.032419458, 0.051065944, -0.013461756, -0.0043139863, -0.056257293, 0.04812594, 0.070030265, -0.055621617, 0.026274594, -0.016143512, 0.05493297, 0.016620269, 0.00943581, -0.008336621, 0.04407351, 0.07824107, -0.0052575674, -0.02536081, 0.022473782, 0.0038438512, -0.047755133, 0.003324054, -0.015335674, -0.040312428, -0.017666485, 0.03504162, 0.039279457, -0.03482973, -0.03512108, 0.0019202702, -0.03864378, -0.050695132, -0.042431347, 0.006227635, -0.029055674, -0.014064323, 0.37971026, -0.040921617, 0.015693242, -0.012640675, 0.018116755, -0.02671162, 0.023678917, -0.039120536, 0.00351277, 0.0015693242, 0.050668646, 0.03602162, -0.006585202, 0.07241405, 0.012157297, 0.016977837, -0.0149913505, -0.02528135, 0.033796754, -0.074321076, 0.013541215, -0.055409726, -0.022513513, 0.026698377, 0.010647567, 0.042007565, 0.028923241, -0.033372972, 0.09233189, 0.036577836, -0.034247026, 0.00069071783, 0.027890269, 0.021202432, 0.017732702, -0.014594053, 0.002148716, 0.013090945, -0.026340809, -0.042696215, -0.029929727, -0.02185135, -0.12204972, -0.02079189, -0.08687567, -0.028684864, 0.0658454, 0.04508, -0.012064594, -0.061130807, 0.02095081, 0.005764121, 0.11908323, -0.0056581753, 0.04378216, -0.003565743, 0.07421513, -0.04248432, 0.010197297, -0.013216756, -0.014726485, -0.027201619, -0.0290027, -0.053529184, 0.01760027, 0.014249729, -0.10403891, -0.071407564, 0.052919995, 0.024407296, -0.007005675, 0.0044364864, 0.006684527, -0.0033853038, -0.05620432, -0.023678917, -0.033664323, -0.007429459, 0.030379998, 0.03594216, 0.035174053, 0.049794592, -0.049979996, -0.0580054, 0.017547296, -0.043755673, -0.010362837, -0.057740536, 0.019904593, 0.045689188, -0.011508377, 0.0013781249, 0.046139456, -0.03490919, -0.03464432, -0.014726485, -0.023427296, 0.0339027, 0.06706378, 0.052893512, -0.017375134, 0.098900534, 0.04709297, 0.04799351, 0.05326432, -0.0019947635, 0.015229729, -0.051728103, -0.006972567, 0.028499458, -0.003896824, -0.03504162, 0.023705404, -0.024831079, 0.023453781, -0.11865945, 0.08623999, 0.02169243, 0.012362567, 0.019494053, 0.02140108, 0.080889724, -0.05175459, 0.02083162, -0.31593078, -0.04982108, 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-0.02095081, -0.066216215, -0.0078995945, -0.019586755, 0.040736213, -0.08629297, -0.0067573646, 0.020460809, -0.011952026, -0.012912162, 0.024566215, -0.022195674, 0.0442854, 0.045265403, -0.013077701, -0.048046485, -0.0044298647, -0.08126053, -0.026433513, -0.015441621, -0.24537079, 0.014752972, 0.025175404, -0.041795675, -0.051860537, -0.002340743, 0.06727567, -0.043331888, 0.03035351, 0.0016338851, 0.012885675, 0.08216108, 0.10393297, 0.002736385, 0.0048006754, 0.034670807, 0.021427566, 0.011779864, -0.043596756, -0.014819188, 0.02230162, -0.055939455, 0.15393946, -0.0456627, 0.018288918, -0.019255674, -0.0049629053, -0.0043139863, 0.057369728, 0.014262972, 0.04399405, 0.037584323, 0.036657296, -0.028949728, -0.050695132, 0.042245943, 0.00003484111, -0.05779351, 0.013375674, 0.012766486, 0.0001269489, -0.007449324, -0.09042486, -0.055727564, 0.07532756, -0.031545404, -0.026963241, 0.015415134, -0.0025228376, -0.025996486, 0.005542297, 0.035359457, -0.037266485, -0.0047079725, -0.08618702, 0.015838917, 0.05342324, 0.041557293, -0.07050702, -0.0011107769, 0.013971621, -0.013825945, -0.042775672, 0.09731135, 0.07161946 ]

Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A.

euronal cultures.

8978752

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0.04800133, 0.058360763, 0.011183176, -0.0640545, -0.009054617, 0.023855686, -0.05040008, -0.020020325, 0.102803506, 0.047368694 ]

Sequence and functional analysis of cloned guinea pig and rat serotonin 5-HT1D receptors: common pharmacological features within the 5-HT1D receptor subfamily.

This study was undertaken to investigate the pharmacology of cloned guinea pig and rat 5-hydroxytryptamine (serotonin; 5-HT)1D receptor sites. Guinea pig; rat; and mouse 5-HT1D receptor genes were cloned; and their amino acid sequences were compared with those of the human; dog; and rabbit. The overall amino acid sequence identity between these 5-HT1D receptors is high and varies between 86 and 99%. The sequence homology is slightly more divergent (13-27%) in the N-terminal extracellular region of these 5-H

8978753

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0.030724304, -0.020416709, 0.04300344, 0.05657929, 0.0063380455, 0.033053104, -0.039748408, -0.00067689066, -0.031253576, 0.02613286, 0.029956857, -0.06843501, -0.044723578, 0.0024743518, 0.03535544, -0.044697113, -0.070393324, 0.04033061, -0.010962569, -0.09918578, -0.031888705, 0.04194489, -0.0010486223, -0.04612615, 0.43104002, 0.02085336, -0.011028728, -0.034561533, 0.03996012, 0.002065819, -0.032709077, -0.016672103, 0.01216005, 0.0017135217, 0.042315383, 0.0074759824, -0.00048048072, -0.0037379912, 0.004763458, -0.004968551, -0.0048660045, 0.04295051, 0.06986405, -0.0066225296, 0.05626173, -0.030803693, -0.012914264, -0.00047965374, 0.043109294, 0.032417975, -0.010512687, -0.025153704, 0.04916947, 0.05631466, -0.021700196, 0.06769403, 0.019239077, -0.024359794, 0.033847015, -0.032629687, -0.03916621, -0.009831248, -0.068329155, -0.0003781408, -0.032391515, -0.030512594, -0.065206446, 0.020509332, -0.038636934, -0.075421415, 0.05546782, -0.023195393, -0.025180167, -0.045199923, 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-0.03382055, 0.0066986126, 0.033211887, -0.01332445, -0.03157114, 0.0014000927, 0.00472707, 0.018643646, 0.020403478, 0.01818053, 0.032894325, 0.054938547 ]

Sequence and functional analysis of cloned guinea pig and rat serotonin 5-HT1D receptors: common pharmacological features within the 5-HT1D receptor subfamily.

T1D receptors. Guinea pig and rat 5-HT1D receptors; stably and separately expressed in rat C6 glial cells; are negatively coupled to cyclic AMP formation upon stimulation with agonists; as previously found for cloned human 5-HT1D receptor sites. The cyclic AMP data show some common pharmacological features for the 5-HT1D receptors of guinea pig; rat; and human: an almost similar rank order of potency for the investigated 5-HT1D receptor agonists; stereoselectivity for the binding affinity and agonist potenc

8978753

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-0.069009386, -0.021255946, 0.005985643, 0.026062896, -0.0674817, 0.043618146, 0.06637544, 0.021255946, -0.011207441, -0.0071643335, -0.0050966856, -0.031264942, -0.06885135, -0.009001511, -0.02442985, -0.03229218, 0.0072104274, 0.036322117, 0.051098555, -0.26676607, 0.017844984, -0.04996596, -0.024561549, -0.02640531, 0.007625274, -0.033029683, 0.025680974, -0.011167931, 0.027419379, 0.04000964, 0.0013416663, 0.063952215, 0.032476556, -0.027208664, -0.04201144, 0.013163146, -0.03429398, 0.031133244, -0.010601633, 0.0488597, 0.0239294, 0.13464732, -0.025048828, -0.037928823, 0.067587055, 0.003356635, 0.026616026, 0.0038455613, 0.026497498, 0.0019359504, -0.021427153, 0.013031448, 0.013354107, 0.07343442, 0.030922528, 0.011576193, 0.004415152, -0.029052425, -0.0034537618, 0.022085639, -0.030922528, 0.006314886, -0.06495311, 0.08286394, -0.013485804, -0.040931523, -0.026076067, -0.0055872584, -0.03561095, 0.022256846, -0.030185023, 0.013301428, 0.040352054, 0.031739052, -0.037402034, 0.0066177896, -0.036032382, 0.0065782806, -0.07011565, 0.035321217, 0.018016191, -0.04701594, 0.10678018, -0.014565722 ]

Sequence and functional analysis of cloned guinea pig and rat serotonin 5-HT1D receptors: common pharmacological features within the 5-HT1D receptor subfamily.

y of R(+)-8-hydroxy-2-(di-n-propylamino)tetralin; and equal 5-HT1D receptor-mediated antagonist potency for methiothepin and the 5-HT2 receptor antagonists ritanserin and ketanserin. In conclusion; the pharmacology of the cloned 5-HT1D receptor subtype seems; unlike the 5-HT1B receptor subtype; conserved among various mammal species such as the human; guinea pig; and rat.

8978753

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0.041426193, 0.038812302, -0.004465395, -0.032792438, -0.06532084, 0.023736233, 0.046970807, -0.007967084, 0.022508496, 0.0028284136, -0.044884976, 0.016858269, -0.0030165345, 0.0064423145, 0.049083043, 0.026218107, 0.08617916, 0.03165711, -0.0011345008, 0.019696584, 0.039076332, -0.05745277, -0.2633956, 0.03487827, -0.020884715, 0.013069449, -0.08396131, 0.00093647884, 0.067485884, 0.024449112, -0.006141981, 0.038469065, -0.061201986, -0.018323632, 0.09943342, 0.0022805529, -0.0043993876, -0.028119119, 0.06516243, -0.010633779, -0.04591469, -0.0042442707, -0.00640271, -0.06088515, 0.18281387, -0.09774364, -0.030178547, 0.027247822, 0.0066997427, 0.017623954, -0.0047690286, 0.020145433, 0.036462445, 0.0140859615, 0.06167724, -0.0142707825, 0.010706387, -0.017095895, -0.054046795, 0.018627265, -0.014838445, -0.01280542, -0.0069835745, 0.083802894, -0.046416346, -0.0148252435, 0.07435065, -0.031973947, -0.031102648, -0.0092014205, 0.055710178, 0.020963924, -0.034297403, -0.0067591495, 0.06305019, -0.011953926, 0.0032624118, -0.030416172, -0.007802065, 0.017003486, 0.033426106, 0.072555244, 0.0009505054, 0.017161904, -0.06685221, 0.09874695, -0.009181618 ]

Implication of Ca(2+)-dependent protein tyrosine phosphorylation in carbachol-induced phospholipase D activation in rat pheochromocytoma PC12 cells.

The mechanism for carbachol (CCh)-induced phospholipase D (PLD) activation was investigated in [3H]palmitic acid-labeled pheochromocytoma PC12 cells with respect to the involvement of protein tyrosine phosphorylation and Ca2+. PLD activity was assessed by measuring the formation of [3H]phosphatidylbutanol in the presence of 0.3% butanol. Pretreatment of cells with the tyrosine kinase inhibitors herbimycin A; genistein; and tyrphostin inhibited PLD activation by CCh. Western blot analysis revealed several ap

8978754

[ -0.03832153, -0.013890562, 0.007673575, 0.0067069298, -0.01079862, 0.000921127, 0.046451945, 0.014936657, -0.03877175, -0.017399617, 0.042532396, -0.03795076, -0.0031349766, 0.005928979, -0.039301418, 0.0038235458, -0.018035218, 0.042505912, -0.09888914, -0.04057262, -0.021928284, -0.0035256073, 0.012506802, 0.021689933, 0.009500932, 0.0396457, -0.026496677, -0.04549854, -0.027251454, -0.17436694, 0.019730158, -0.027039586, 0.03408418, -0.03583209, 0.0058727018, -0.060964867, 0.021835592, 0.000098537, 0.009361894, -0.037421092, 0.08437622, 0.020868946, -0.034031212, 0.014195121, 0.012884191, 0.027383871, 0.039513282, -0.035434835, 0.014618856, 0.024867944, 0.03262759, -0.07558372, -0.009739283, 0.028045956, -0.025622724, 0.008309177, 0.05450291, 0.04626656, 0.010858208, 0.05821059, -0.026258325, 0.006879072, -0.09539333, -0.014830723, 0.10450363, 0.02466932, 0.062024202, -0.07214087, 0.027595738, 0.025887556, -0.02668206, 0.041049324, 0.0219018, 0.12807389, -0.016909672, -0.05577411, -0.0025688931, -0.08739533, 0.018392745, -0.018644338, -0.030879684, -0.04202921, 0.01518825, -0.00036538864, -0.0021534343, 0.0033120846, -0.0951285, -0.06838023, 0.0055118646, 0.03747406, 0.045048323, 0.0036977495, 0.0067069298, 0.011473948, -0.07659009, 0.009342032, 0.021795867, -0.0068989345, -0.010745654, 0.39576843, 0.012387627, 0.02567569, -0.044968873, -0.024245584, -0.025556514, -0.03254814, -0.012467077, -0.048994355, 0.020326035, 0.06430178, 0.06657936, 0.0036580244, 0.016605113, 0.0005069095, -0.023093555, -0.017664451, 0.04989479, 0.03162122, -0.050689295, 0.02305383, -0.0018356331, -0.088666536, 0.015559018, -0.06943957, 0.036600105, 0.05198698, 0.018167635, 0.070392966, 0.049762372, -0.002598687, 0.0521194, 0.027966507, 0.025794866, 0.007964893, 0.024775254, 0.0021915042, -0.05969366, -0.044121403, 0.0013208613, -0.0057005594, -0.00470412, -0.08532962, -0.026086183, -0.07388878, -0.016327037, 0.06663232, -0.03731516, 0.0022891618, 0.022325534, -0.018233845, -0.0030422846, 0.065414086, -0.062553875, 0.01627407, 0.0023173005, 0.021067573, -0.043141514, 0.01064634, -0.016062204, -0.0051477174, -0.08273425, -0.0034064318, -0.060753, 0.11440843, 0.036891423, -0.0700222, -0.009077197, 0.012036721, 0.025503548, 0.0059488416, -0.017134782, 0.036520656, -0.0148836905, 0.0040850695, -0.038533397, -0.02382185, 0.009779008, -0.0070379726, 0.040069435, 0.036441207, -0.006230228, -0.041155256, 0.016234346, 0.034428466, 0.022484437, -0.0074219825, -0.0612297, 0.067903526, 0.04549854, 0.012950399, -0.042770747, 0.052304782, -0.0521194, 0.07023407, -0.027728155, -0.10773461, -0.025741898, -0.009163268, -0.051907532, -0.04404195, 0.096876405, 0.064513646, 0.022855204, 0.085806325, -0.0014598994, 0.01835302, 0.010553649, -0.006624169, 0.09915398, -0.006332851, -0.050212592, 0.010467578, -0.0038103042, 0.0068923137, -0.040678553, 0.036759008, -0.01141436, -0.032654073, 0.04774963, -0.009779008, 0.05251665, 0.0025622724, -0.0887195, -0.29725006, -0.021478064, -0.028284308, -0.03792428, 0.044227336, 0.031727154, -0.026880685, 0.010315298, 0.021319164, -0.09105004, 0.02690717, 0.060911898, -0.014274571, -0.044598103, -0.046849195, 0.02382185, -0.021266198, -0.036573622, 0.003717612, 0.0022014354, 0.024325034, -0.008302556, -0.044094916, 0.0038665815, 0.053470053, -0.037977245, 0.13040443, 0.057204217, 0.00078333035, 0.024046957, -0.012460456, 0.05352302, -0.030350016, -0.05037149, -0.052172367, -0.017677693, -0.04549854, -0.02028631, 0.005329791, 0.05198698, 0.00069643155, 0.016393246, 0.007938409, -0.050795227, -0.0002720759, -0.0054953126, 0.058263555, -0.016936157, 0.03625582, -0.08321095, -0.013374134, -0.019412357, -0.029237712, 0.005674076, 0.014751273, -0.061335634, -0.062289037, -0.027887056, -0.029423095, 0.0021252956, 0.048914902, 0.04078449, 0.030906169, -0.032812975, 0.048570618, -0.010136534, -0.023305422, 0.044942386, 0.06265981, -0.0047835703, 0.031012101, 0.08739533, -0.011195872, 0.012983504, 0.02282872, 0.012453835, 0.020988122, -0.04171141, -0.019889059, 0.051616214, -0.009659832, -0.03384583, 0.030747266, 0.0052569616, -0.002729449, 0.03747406, -0.0028982807, -0.019293182, 0.025357889, -0.01950505, 0.05535038, -0.0036414722, 0.0006442923, -0.008084068, 0.013036471, -0.03424308, -0.2682242, 0.002244471, -0.026999861, 0.018776756, -0.07166418, 0.00048249506, 0.02466932, 0.02521223, 0.0033038084, 0.013466827, 0.025887556, -0.0023007484, 0.09173862, -0.013281442, -0.030826718, 0.053470053, 0.091420814, 0.0070909397, -0.06313651, -0.028787494, 0.031886056, -0.04311503, 0.1824179, -0.04266481, 0.02645695, 0.03622934, 0.025490306, 0.03972515, -0.045895793, 0.017002365, 0.026748268, 0.027119037, -0.012381005, -0.037765376, 0.0029959385, -0.004535288, 0.0064983726, 0.00019697055, 0.027754638, -0.0131093, -0.04743183, 0.0398046, -0.08151601, -0.042135146, 0.082522385, -0.057204217, -0.05831652, -0.025397614, -0.013718419, -0.011937408, -0.019266699, 0.0020259828, 0.068803966, -0.008474699, -0.020710045, 0.018286811, -0.06769166, 0.047166996, 0.018723788, 0.04473052, 0.0613886, 0.019054832, 0.011056834, 0.05535038, 0.036361754 ]

Implication of Ca(2+)-dependent protein tyrosine phosphorylation in carbachol-induced phospholipase D activation in rat pheochromocytoma PC12 cells.

parent tyrosine-phosphorylated protein bands (111; 91; 84; 74; 65-70; 44; and 42 kDa) in PC12 cells treated with CCh. Phosphorylation of the 111-; 91-; 84-; and 65-70-kDa proteins peaked within 1 min; and their time-dependent changes seemingly correlated with that of PLD activation. Others (74; 44MAPK; and 42MAPK kDa) were phosphorylated rather slowly; and maximal tyrosine phosphorylation was observed at 2 min. Herbimycin A inhibited PLD activity and tyrosine phosphorylation of four proteins (111; 91; 84; a

8978754

[ -0.013334105, -0.033926856, 0.022161469, -0.010356199, -0.0039517074, -0.03677182, -0.014344466, 0.032384727, -0.033368498, -0.03025765, 0.09858995, -0.025498318, -0.0069728196, -0.011885035, -0.060036708, -0.011944858, -0.05812234, 0.04873662, -0.05386819, 0.0053874836, 0.017894024, -0.013560107, -0.0042740926, 0.009418957, 0.024142308, 0.06391862, -0.017309077, -0.041584328, -0.02606997, -0.18665089, 0.053097125, 0.010868027, 0.02940682, -0.023756776, -0.00687976, -0.060302593, 0.0033518057, 0.0020456484, -0.03791512, 0.06897043, 0.06663064, -0.027133508, -0.023942895, 0.051395465, -0.015328239, 0.040095374, 0.009904196, -0.006141931, -0.0089736, 0.022174763, -0.010150138, -0.027279744, 0.043791167, 0.036665466, -0.021749347, 0.05897317, 0.036505934, 0.069342665, -0.016631072, 0.047114722, -0.031321187, 0.010615436, -0.097526416, 0.022972416, 0.0752453, 0.042355392, 0.025777496, -0.07907403, 0.061206598, 0.043737993, -0.09997255, 0.077159666, 0.036186874, 0.11592562, 0.008242418, 0.0047094785, -0.060408946, -0.06636476, 0.03488404, -0.059451763, -0.0012014654, -0.047779433, -0.031161657, -0.02836987, -0.053761836, 0.006497551, -0.05264512, -0.053469364, 0.015288356, 0.03541581, 0.029353643, 0.030683065, 0.03536263, -0.010017197, -0.06966172, 0.02443478, -0.0015786889, -0.027186684, 0.060355768, 0.397125, -0.02818375, 0.014371054, -0.040441025, -0.0006534941, -0.0036758524, -0.037649237, -0.06923631, -0.04961404, 0.027279744, 0.051820878, 0.0618979, -0.01631201, 0.035974167, -0.0041610915, -0.057324685, 0.018665088, 0.008468419, 0.013772815, -0.051342286, 0.007717296, -0.014636938, -0.04030808, -0.0035462338, -0.030523535, 0.08689104, 0.03379391, 0.029486585, 0.056473855, -0.00010614606, -0.020419925, 0.054453135, 0.03227837, 0.003208893, 0.018120024, -0.0045632417, 0.03791512, -0.024820313, -0.055357143, 0.018000377, 0.0111937355, -0.02006098, -0.084710784, -0.027279744, -0.0028283459, -0.035336044, 0.04905568, -0.021669582, 0.04663613, 0.0047792727, 0.0027352863, -0.022254528, 0.074819885, -0.043365754, 0.036426168, -0.016710838, 0.06668382, -0.042142686, 0.007112409, 0.0020556191, -0.0013510253, -0.049268387, 0.027971044, -0.017056488, 0.08481714, 0.018771442, -0.100770205, -0.0069462312, 0.036133695, 0.04583848, -0.03315579, -0.01879803, -0.03126801, -0.000501026, 0.005247894, -0.04961404, -0.012961866, -0.045705535, 0.005257865, 0.03126801, 0.027971044, 0.012303803, -0.05679292, 0.002191885, 0.025910439, 0.014597056, -0.06349321, -0.07561754, 0.03743653, 0.015634006, 0.008687775, -0.003036068, -0.015328239, -0.0683323, 0.049693804, 0.012051213, -0.06290826, -0.028742108, -0.0186385, -0.0404942, -0.036479346, 0.108321324, 0.018904384, 0.03398003, 0.07583024, 0.006979467, 0.0312946, 0.05503808, -0.013533519, 0.047460373, -0.013247693, -0.040015608, 0.03299626, -0.04565236, 0.011120617, -0.036692053, 0.02358395, -0.03554875, 0.0064510214, 0.04089303, -0.0045865066, 0.0379683, -0.052246295, -0.072214216, -0.29757786, -0.0345118, -0.03366097, -0.017614845, 0.010309669, 0.030656477, -0.03201249, 0.039164778, 0.01659119, -0.03504357, 0.0009081616, 0.085242555, -0.011831858, -0.0499331, -0.040015608, -0.0012014654, 0.0086944215, 0.016936839, 0.010462553, -0.008893834, 0.010602143, 0.02521914, -0.055995263, 0.043791167, 0.071522914, -0.044509057, 0.11858446, 0.032358136, 0.0049853334, 0.024089132, 0.00016638551, -0.009000189, -0.011745445, -0.017216017, -0.025777496, -0.055250786, -0.03179978, -0.016910251, -0.019024031, 0.03823418, 0.032916494, -0.038313948, -0.052724887, -0.06822595, 0.0165646, -0.035256278, 0.0075577656, 0.008873893, 0.03262402, -0.023876423, 0.017043194, -0.02632256, -0.028954817, -0.010987675, -0.008614656, -0.03690476, -0.048258025, -0.059239056, -0.04937474, -0.051422052, 0.08050981, 0.0010460891, 0.033820502, 0.0065008746, 0.04341893, -0.014410937, -0.014942706, 0.07407541, 0.045492828, -0.035149924, 0.004510065, 0.13155963, -0.04730084, 0.029646115, 0.03148072, 0.008322183, 0.0043106517, -0.025033021, -0.023105359, 0.015766948, 0.025551496, -0.024341721, 0.03177319, -0.0037223822, -0.06264237, 0.009305956, 0.003948384, -0.014690116, 0.05934541, 0.02248053, 0.039031837, -0.019289916, 0.0102963755, 0.041797034, 0.031241423, -0.0126561, -0.2560999, 0.008156005, -0.016046125, 0.015753653, -0.091517426, -0.017242607, 0.053947955, -0.012543099, 0.044163406, -0.006221696, -0.012503216, 0.0025558143, 0.095824756, -0.0017947201, 0.024195485, 0.04222245, 0.0879014, -0.017933905, -0.022467235, -0.06849183, 0.049454506, -0.059239056, 0.16623096, -0.024062542, -0.0045034178, 0.03379391, 0.01907721, -0.00014571715, -0.041664094, 0.0152218845, 0.008980247, 0.03693135, 0.011738799, -0.074819885, -0.0078103556, -0.033235557, 0.006460992, 0.018731559, 0.020619338, -0.028688932, -0.017827552, 0.044003874, -0.074926235, -0.021084636, 0.087848224, -0.029539762, -0.059451763, -0.016365187, -0.0056998977, -0.02257359, -0.009684841, 0.003149069, 0.047274254, -0.029114347, -0.038500067, 0.012117684, -0.045040824, 0.071150675, 0.030816007, 0.064237684, 0.07226739, 0.0077571785, 0.007956592, 0.089656234, -0.0037456471 ]

Implication of Ca(2+)-dependent protein tyrosine phosphorylation in carbachol-induced phospholipase D activation in rat pheochromocytoma PC12 cells.

nd 65-70 kDa) in a preincubation time- and concentration-dependent fashion. In Ca(2+)-free buffer; CCh-induced [3H]phosphatidylbutanol formation and protein tyrosine phosphorylation were abolished. A Ca2+ ionophore; A23187; caused PLD activation and tyrosine phosphorylation of four proteins of 111; 91; 84; and 65-70 kDa only in the presence of extracellular Ca2+. Extracellular Ca2+ dependency for CCh-induced PLD activation was well correlated with that for tyrosine phosphorylation of the four proteins liste

8978754

[ -0.016608892, -0.020401059, -0.031050835, -0.039216544, -0.02735116, 0.043814708, -0.0077627087, 0.00456183, 0.010887612, -0.0013097506, 0.03165864, -0.034036998, 0.049311366, -0.041092806, -0.023083322, 0.051081926, -0.041357066, 0.0021273124, -0.06939531, -0.010933857, 0.014851548, -0.044501793, -0.03136795, 0.031473655, 0.012955465, 0.01968755, -0.028434636, -0.097724244, -0.014468367, -0.13910773, 0.03390487, 0.016357843, 0.03662677, -0.04368258, 0.03208146, -0.07954299, -0.005883142, 0.022845486, -0.009011349, 0.0027830135, 0.04606094, -0.026782995, -0.035490442, -0.061625995, 0.059881862, 0.008568709, -0.05660501, -0.0124731865, 0.031024408, -0.035411164, -0.017520599, -0.08218561, -0.014283383, 0.040115036, -0.020771027, 0.03985077, 0.07166797, 0.02003109, 0.03260998, 0.02562024, 0.026796209, 0.055865075, -0.13139127, 0.035833985, 0.028143948, 0.00026673987, 0.0335349, -0.045109596, 0.023070108, 0.023189027, 0.008278021, 0.048360024, 0.08429971, 0.11902379, -0.0076371836, 0.06685839, -0.0033924687, -0.052720353, -0.024431061, -0.037419558, -0.040405724, -0.016186073, 0.017282762, 0.016357843, 0.016529614, 0.04986632, -0.0925447, -0.08165709, -0.011720038, -0.012902613, 0.010293021, 0.02231696, 0.026148766, 0.010629956, -0.002964694, 0.0035543295, 0.010339267, -0.07579046, 0.079225875, 0.3786352, -0.04899425, -0.010187316, -0.0054669287, 0.012360875, -0.028672472, -0.003162891, -0.05097622, -0.08176279, -0.010055185, -0.013702006, 0.053486712, -0.015393286, 0.06754547, -0.029412407, -0.03438054, 0.039533656, 0.01888155, -0.03686461, -0.040590707, 0.029570965, 0.0563936, -0.0060152733, -0.0335349, -0.03340277, 0.06728121, -0.011184907, 0.018128403, 0.05279963, 0.03607182, -0.020057518, 0.0260827, 0.040854968, 0.022515157, -0.002308993, -0.04577025, -0.022475518, 0.0018564435, -0.08889788, -0.048888545, -0.036891032, 0.019832894, -0.08799938, -0.035252605, -0.049390644, -0.044607498, 0.078274526, -0.009328463, 0.060357537, -0.049126383, 0.03916369, -0.018511582, 0.057186387, -0.029200997, -0.01744132, -0.034274835, 0.016159646, -0.045875955, 0.018656926, 0.03297995, 0.025567388, 0.017573452, -0.0038152887, -0.008330872, 0.10004975, 0.05013058, -0.08614955, 0.03755169, -0.0008613303, 0.06627701, -0.044818904, 0.00019809359, -0.033984147, 0.021008862, 0.038582314, 0.004951617, 0.010451579, -0.075473346, -0.0018547919, 0.06315872, 0.0119578745, 0.057503503, -0.07277787, -0.059987567, 0.024801027, 0.015617909, -0.033640604, -0.045479562, 0.009024561, 0.04725012, 0.034750506, -0.01824732, 0.051002648, -0.035701852, -0.025778798, -0.009632365, -0.052138973, -0.05097622, -0.011435956, 0.036573917, -0.062313076, 0.037419558, 0.013503809, 0.05602363, 0.010649775, 0.027615422, 0.00089518895, 0.033878442, -0.082449876, 0.052429665, 0.042519823, -0.007273823, -0.06511426, -0.02137883, 0.059776157, -0.048280742, 0.06754547, -0.0017969845, -0.004492461, 0.067968294, -0.0028788086, 0.054068092, -0.030152341, -0.0101608895, -0.26637653, -0.014930827, 0.0129884975, -0.03107726, -0.024840668, 0.018062336, 0.02721903, 0.0765304, -0.017005287, -0.04754081, 0.0128761865, 0.032107882, -0.060146127, 0.023810044, -0.043154053, 0.009037775, 0.008370512, 0.013114022, 0.0077032493, 0.015591483, 0.0056519127, 0.05351314, -0.017124204, -0.013391498, 0.038503036, -0.04661589, 0.15834604, 0.031737916, 0.0043702396, 0.008918856, 0.047567233, -0.0013023182, -0.048333596, -0.022237683, 0.005549511, 0.04711799, -0.010002333, -0.010273201, -0.028038243, 0.06474429, 0.013583088, -0.05486088, 0.0066197733, -0.09270325, 0.032953523, -0.010279808, -0.03823877, 0.013166875, 0.018101975, 0.054120943, 0.027958963, -0.037630968, -0.010418545, 0.041938446, -0.019846108, -0.017163845, -0.04513602, 0.014032334, 0.0073068556, 0.010874398, 0.07843309, -0.013873776, 0.021259911, -0.07912017, 0.05940619, -0.041515626, -0.00016093168, 0.025091717, -0.019304369, -0.047990054, 0.0191326, 0.07542049, -0.0037095838, 0.0057774372, -0.03184362, 0.065801345, -0.043286186, -0.016489975, -0.05803203, -0.0038251984, 0.039190117, -0.08049433, 0.011356677, 0.05512514, 0.033006378, 0.011819136, 0.02721903, 0.0013791195, -0.018524796, -0.015657548, 0.038582314, -0.029306702, 0.0011817485, -0.019172238, -0.033297066, -0.010484612, -0.30992696, -0.0044693383, -0.057926323, 0.016014302, -0.0039738463, 0.046008088, 0.04304835, 0.024787815, -0.0038185918, 0.027826833, 0.0113698905, -0.018498369, 0.10258667, -0.024629258, 0.011468989, 0.05343386, 0.06004042, -0.059776157, 0.034089852, -0.054120943, 0.078274526, -0.008225168, 0.14608426, 0.0043107807, 0.03641536, 0.013114022, -0.013754859, 0.030258046, -0.000369348, -0.03781595, -0.008112856, 0.05303747, 0.031975754, -0.08725945, -0.072460756, 0.04754081, 0.028963162, 0.005694855, -0.019634698, -0.014270171, -0.0063852407, -0.008013758, -0.06305301, -0.026650865, 0.0883165, 0.0008026971, -0.038846575, -0.016661745, 0.040907823, 0.028461061, -0.016542828, 0.022713354, 0.031737916, 0.00165164, -0.0040465184, -0.048914973, -0.04093425, -0.007908053, 0.0047336007, 0.020903157, 0.021656305, -0.024431061, 0.016622106, 0.10797762, -0.058137733 ]

Implication of Ca(2+)-dependent protein tyrosine phosphorylation in carbachol-induced phospholipase D activation in rat pheochromocytoma PC12 cells.

d above; especially the 111-kDa protein. These results suggest that Ca(2+)-dependent protein tyrosine phosphorylation is closely implicated in CCh-induced PLD activation in PC12 cells.

8978754

[ -0.0835234, -0.009353985, 0.011798475, -0.0055911923, -0.02305373, -0.018959707, 0.017131306, -0.01217608, -0.013752743, -0.04056927, 0.073082976, -0.04814785, -0.01416347, -0.02160956, -0.04321912, -0.038475882, -0.032593206, 0.04160271, -0.06921419, 0.009194993, -0.012898165, -0.025716834, 0.0019476428, 0.012653054, 0.037892915, 0.053712543, -0.0013613625, -0.07218203, -0.037574932, -0.18972956, 0.039641816, 0.035163563, 0.02853893, -0.03288469, -0.0148789305, -0.011056516, -0.0454185, 0.014017728, -0.0153956525, 0.038555376, 0.0634905, -0.0028535617, 0.0013514255, 0.0028535617, 0.042212177, 0.012215828, -0.027584981, 0.018191248, 0.04671693, 0.03614401, -0.04327212, 0.0096587185, 0.018058756, 0.121999286, -0.007320222, 0.027293498, 0.053103074, 0.04451755, 0.0046008094, 0.027041761, 0.019993149, 0.034236114, -0.10387428, 0.03651499, 0.075255856, 0.009996574, -0.013885235, -0.06879021, 0.03288469, 0.045709983, -0.047087908, 0.04454405, 0.007379844, 0.10387428, -0.028777415, 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0.0014797779, 0.0018499295, -0.06629935, 0.041337725, -0.036832973, 0.051327676, -0.027266998, -0.033865135, 0.081297524, 0.027531983 ]

Energy stress-induced dopamine loss in glutathione peroxidase-overexpressing transgenic mice and in glutathione-depleted mesencephalic cultures.

The role of the glutathione system in protecting dopamine neurons from a mild impairment of energy metabolism imposed by the competitive succinate dehydrogenase inhibitor; malonate; was investigated in vitro and in vivo. Treatment of mesencephalic cultures with 10 microM buthionine sulfoxamine for 24 h reduced total glutathione levels in the cultures by 68%. Reduction of cellular glutathione per se was not toxic to the dopamine population; but potentiated toxicity when the cultures were exposed to malonate.

8978755

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-0.041744255, 0.022419682, 0.010436064, 0.03735291, -0.009754876, 0.04007766, -0.0029925976, 0.044469006, -0.024139185, -0.016110426, 0.047960922, 0.06528823 ]

Energy stress-induced dopamine loss in glutathione peroxidase-overexpressing transgenic mice and in glutathione-depleted mesencephalic cultures.

In contrast; transgenic mice overexpressing glutathione peroxidase (hGPE) that received an intrastriatal infusion of malonate (3 mumol) into the left side had significantly less loss of striatal dopamine than their hGPE-negative littermates when assayed 1 week following infusion. These studies demonstrate that manipulation of the glutathione system influences susceptibility of dopamine neurons to damage due to energy impairment. The findings may provide insight into the loss of dopamine neurons in Parkinso

8978755

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Energy stress-induced dopamine loss in glutathione peroxidase-overexpressing transgenic mice and in glutathione-depleted mesencephalic cultures.

n's disease in which defects in both energy metabolism and the glutathione system have been identified.

8978755

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The tau protein in human cerebrospinal fluid in Alzheimer's disease consists of proteolytically derived fragments.

Previous studies have shown that the levels of the microtubule-associated protein tau in the CSF of patients with Alzheimer's disease (AD) are elevated compared with age-matched controls. In spite of these findings; the nature of tau in CSF has not been well documented. In the present study; tau was immunoprecipitated from CSF of patients with AD or acute stroke; as well as normal elderly controls; followed by immunoblot analysis. In all cases; CSF tau consisted primarily of a band migrating at 26-28 kDa. I

8978756

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0.013561296, 0.04212602, 0.0033605555, -0.0064796535, 0.07964781, -0.012582237, 0.027493048, -0.0075480193, 0.0056527453, -0.01006182, -0.0021863456, 0.019025506, -0.054509796, 0.0018109293, 0.0035854746, 0.04072358, -0.03820978, -0.109972194, 0.038077474, 0.029504089, -0.15739042, -0.020150103, -0.0013867252, -0.024502948, -0.02631553, 0.3765939, -0.024264798, 0.0131974565, -0.015823718, 0.007567865, 0.01413021, -0.009532599, 0.022730056, 0.015003424, 0.0027188745, -0.020785168, 0.03791871, 0.03995621, 0.026117072, -0.0097442875, -0.027122593, 0.034028932, 0.02831334, 0.023748808, -0.045857027, 0.090020545, 0.004825837, -0.018337518, -0.011497334, -0.030006848, 0.060384154, 0.05255168, -0.047524076, 0.07874814, 0.09033808, 0.0022872284, 0.08139424, 0.08864457, -0.015228343, 0.014474203, -0.029477628, 0.02161869, -0.011384874, -0.07144488, -0.0117156375, -0.056044538, 0.024529409, -0.008778458, -0.07620787, -0.03355263, -0.05366304, 0.08351112, -0.054562718, 0.028551491, -0.05339843, 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-0.0659939, -0.017570147, 0.015440032, -0.04096173, -0.020996856, -0.0068137245, 0.015942791, -0.006234889, -0.046809625, 0.09150237, 0.015466494 ]

The tau protein in human cerebrospinal fluid in Alzheimer's disease consists of proteolytically derived fragments.

n AD and stroke patients; several smaller tau fragments were also detected. No intact tau was detected in any of the CSF samples examined. Further immunoprecipitation studies showed that the majority of the tau fragments contained the amino terminus of the molecule. Treatment of CSF tau with alkaline phosphatase did not alter the electrophoretic properties of the fragments. These studies clearly demonstrate that CSF tau is truncated rather than intact.

8978756

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-0.041066185, 0.0055283974, -0.046182714, 0.014559342, 0.0493705, 0.0044903583, 0.036190744, 0.0058096726, -0.005083045, 0.048406128, -0.0074738846, 0.058933858, -0.023345843, 0.032627925, -0.023024386, -0.031529613, -0.028824015, -0.01947496, 0.033029746, 0.018899016, -0.25695163, 0.0055987164, 0.015456744, -0.05502279, -0.07564964, -0.055129945, -0.044200394, -0.04535228, 0.019180292, 0.018256102, 0.030886699, 0.03190465, 0.055129945, 0.043503903, 0.026386295, -0.036646143, 0.087007806, -0.016675603, -0.008418166, -0.044012874, -0.016688997, -0.026707752, 0.11861778, -0.013594969, -0.05652293, 0.06750605, -0.03828022, -0.0036264414, -0.05277259, 0.02197965, 0.011733195, -0.010132605, -0.015242439, -0.08416826, 0.03356551, 0.03439594, -0.01663542, 0.044682577, -0.0014231188, -0.012074743, -0.052129675, 0.03241362, 0.027377455, 0.016126446, 0.11647473, 0.024403974, -0.011713104, -0.056790806, -0.035601407, -0.040342905, -0.040744726, 0.010206273, -0.018564165, -0.047388177, -0.012925266, 0.008123497, -0.015443349, -0.061826974, 0.012905175, -0.02089473, 0.002811078, -0.037905186, -0.04880795, 0.087275684, -0.013454332 ]

Conformations of beta-amyloid in solution.

nan

8978758

[ -0.027652219, 0.015561098, -0.013947155, 0.015399704, 0.010820141, 0.010322509, 0.014296843, 0.02287764, -0.033112727, 0.02227241, -0.0008279863, 0.02708734, -0.018708287, 0.0098786745, 0.055412035, -0.004445067, 0.021774778, -0.034861162, 0.0083857775, -0.008136962, 0.034242485, -0.008991006, -0.008722016, 0.016179776, 0.049494244, -0.0007170277, -0.024330188, 0.039299507, -0.032547846, -0.08290286, 0.004337471, 0.0038465636, -0.025849983, 0.030799408, -0.017376784, 0.04599737, -0.018224103, -0.0008212615, -0.05196896, 0.07714646, 0.011364847, 0.04169352, -0.0142161455, 0.015628345, -0.064772904, 0.021599934, 0.04742302, -0.03725518, 0.004734232, 0.071228676, 0.006859257, -0.09559921, -0.0052957498, 0.06557988, -0.04454482, 0.0025554094, -0.04935975, 0.054416772, 0.0253927, 0.03779316, 0.04532489, 0.076823674, -0.14590043, -0.00060943153, 0.07983637, 0.0054100705, 0.012514781, -0.09559921, 0.057133574, 0.09979546, -0.032870635, -0.024289839, -0.02591723, -0.018842781, 0.055950016, 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0.039810587, -0.061545018, 0.032897532, 0.09237132, -0.03585643, 0.027248735, 0.040509965, -0.015601447, 0.043818545, -0.026818348, -0.01156659, -0.016516015, 0.06504189, -0.03244025, -0.05729497, -0.025312003, 0.007525008, 0.025554094, 0.019300066, -0.30385163, 0.034296285, 0.0042265127, -0.052668333, -0.024128444, 0.032520946, -0.01943456, 0.039111212, 0.035103254, 0.014821375, -0.007525008, 0.042204604, 0.0564342, 0.0052419514, 0.0025032924, 0.011600214, 0.10302335, -0.0050536585, -0.056918383, -0.007128247, -0.03265544, -0.022474153, 0.15084985, -0.019057974, 0.0056185382, 0.049090758, -0.0479072, 0.013086386, 0.024303287, 0.024948865, 0.01747093, 0.01834515, -0.04478691, -0.0902194, -0.0011028609, 0.04145143, -0.056219008, -0.04029477, -0.006714674, -0.012736699, -0.061276026, -0.009596235, -0.019932194, -0.020376027, 0.12728629, 0.04736922, -0.07736166, -0.009804702, -0.0059884, 0.015130714, -0.05331391, 0.0023654348, -0.008143686, -0.013328478, -0.07531733, 0.002409146, -0.0366096, -0.038196646, 0.036797896, -0.0281633, 0.011331223, -0.034565274, -0.050086025, 0.02340217, -0.015372805 ]

L-(-)-desmethylselegiline, a metabolite of selegiline [L-(-)-deprenyl], protects mesencephalic dopamine neurons from excitotoxicity in vitro.

Selegiline [L-(-)-deprenyl]; a monoamine oxidase B inhibitor; has been used in the treatment of Parkinson's disease as a putative neuroprotective agent. Selegiline is metabolized rapidly in the gastrointestinal tract and liver to desmethylselegiline (DMS) and methamphetamine. We have previously shown that selegiline protects dopamine neurons in mesencephalic cultures from toxicity resulting from activation of glutamate receptors. In the present study we examined whether DMS has similar neuroprotective effec

8978757

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-0.045864183, -0.014830573, -0.010833114, 0.0064092595, -0.025317242, 0.02013387, 0.04978169, 0.0053232834, -0.02295874, -0.05292636, -0.041626874, -0.039867993, -0.05186037, 0.0050934292, 0.046956822, -0.0076284846, -0.052526616, 0.024877522, -0.014390853, -0.052206818, -0.002120319, 0.016003162, 0.025383865, 0.0015132049, 0.39164442, -0.010420044, -0.01925443, -0.05687052, -0.036030434, 0.02101331, -0.024171304, 0.03144668, 0.046423826, 0.04823601, -0.028115463, 0.015283619, -0.029794397, 0.038642105, -0.042506315, -0.05665732, 0.051673822, 0.06299996, -0.030460639, -0.031100232, 0.0035344202, 0.028648458, -0.016362933, 0.011939079, 0.013644661, 0.001257534, 0.0012017362, 0.044451747, 0.04192002, 0.024717623, -0.009307418, 0.057510115, 0.03616368, -0.013578037, -0.005766335, 0.009993648, 0.03416495, 0.028568508, 0.028195413, -0.00934073, 0.06630453, 0.011372771, -0.0047736326, 0.0046803583, -0.07056848, -0.015030446, 0.07605832, -0.026676377, 0.084906034, -0.06566493, -0.035550736, 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-0.0014265933, -0.0015739995, 0.012845169, 0.022265848, -0.04325251, 0.0195609, -0.014524102, -0.032805815, 0.12397453, 0.010393394 ]

L-(-)-desmethylselegiline, a metabolite of selegiline [L-(-)-deprenyl], protects mesencephalic dopamine neurons from excitotoxicity in vitro.

ts. Our data show that DMS protects dopamine neurons from N-methyl-D-aspartate receptor-mediated excitotoxic damage. The efficacy of DMS is greater than that of selegiline; as it can cause protection at lower concentrations and provide significantly greater levels of protection at the same concentrations. Our results suggest that DMS might be the active compound responsible for the neuroprotective properties of selegiline.

8978757

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Report of the second international workshop on human chromosome 1 mapping 1995.

nan

8978760

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-0.067289576, 0.025400877, -0.012593375, 0.027314642, 0.01667518, -0.0076684416, 0.031690873, -0.012794119, 0.12537166, 0.02329975 ]

Report of the first international workshop on human chromosome 10 mapping 1995.

nan

8978759

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-0.05614882, -0.00285528, -0.029894296, 0.029626666, 0.009099428, -0.0097216675, 0.022869002, -0.0071925623, 0.15319154, -0.01328784 ]

Microdeletions in interval 6 of the Y chromosome detected by STS-PCR in 6 of 33 patients with idiopathic oligo- or azoospermia.

It has been proposed that interval 6 of the human Y chromosome contains the gene or genes that control spermatogenesis (AZF; azoospermia factor). We have studied this region in 33 patients with oligo- or azoospermia; using PCR amplification of the YRRM1 (RBM1) gene and of 13 sequence-tagged sites (STSs); all mapping within interval 6. Six of the 33 patients showed no amplification of specific STSs; whereas there was no failure of amplification in normal male controls. We deduce that these six patients had m

8978761

[ 0.014022827, -0.0006508573, 0.08432376, -0.0042895707, 0.020547245, -0.016157607, 0.08208224, 0.095264494, -0.04720529, -0.027832177, -0.010587168, 0.0063776514, 0.037652157, 0.034823578, -0.02030708, 0.014769999, 0.049420126, -0.018986188, -0.075304314, -0.009179548, -0.008605827, 0.00419951, 0.06954041, -0.030660758, 0.038079113, -0.009479751, -0.058492932, -0.0050300723, -0.018959502, -0.14580537, -0.0011399385, 0.00093730126, 0.0034756865, 0.0064243493, -0.15978818, 0.012975452, -0.051288057, 0.04539073, -0.03789232, 0.0072182203, 0.06601803, 0.06409673, -0.048299365, 0.05254224, -0.00049700314, 0.010273622, -0.057372175, 0.014956793, 0.025350496, -0.025790794, 0.06628487, 0.0009331317, -0.005767238, 0.062282167, 0.010720591, -0.010700578, 0.0025717411, 0.011414395, -0.057745762, 0.0159041, 0.014743315, 0.08330973, -0.12274977, 0.031434614, 0.033009015, -0.018132277, -0.012301662, -0.0011374367, 0.04867295, 0.09681221, -0.0041728253, 0.020507216, 0.0021014228, 0.048326053, 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0.021281075, -0.09393026, -0.029513314, -0.000612498, 0.06431021, 0.0042328658, -0.039386667, 0.014583207, -0.036638137, 0.05865304, -0.015637254 ]

Microdeletions in interval 6 of the Y chromosome detected by STS-PCR in 6 of 33 patients with idiopathic oligo- or azoospermia.

icrodeletions in interval 6 of the Y chromosome that correlated with the oligo- or azoospermia of these individuals. On biopsy of the testis; two of these patients showed a low number of germ cells; and four showed arrest with spermatides. We conclude that PCR amplification of Y-specific regions is a powerful and very sensitive tool for screening infertile men.

8978761

[ -0.064655654, -0.014803585, 0.009035521, 0.01823108, 0.014070074, 0.026846502, 0.00849539, 0.05273277, -0.010842626, -0.09074198, 0.029207073, -0.0033224712, 0.0057180515, 0.040089708, -0.022045339, -0.016777396, -0.011182708, -0.051665846, -0.034835104, -0.024205862, -0.013990055, -0.016617358, -0.046224527, -0.037662454, 0.08908824, 0.008048615, -0.040143054, 0.03515518, -0.039022785, -0.18980597, 0.03883607, 0.052892808, -0.019298006, -0.065989316, -0.048945185, -0.03294131, -0.0039409543, -0.012409672, -0.040169727, 0.030567402, -0.04155673, 0.05139911, 0.025539517, 0.013256543, 0.008528732, -0.0128031, -0.07617845, 0.016190587, 0.049291935, 0.03966294, 0.0037108986, -0.04137002, -0.008375362, 0.04112996, 0.032461192, 0.050038785, 0.0384093, -0.00043968981, -0.0064782356, 0.021738598, 0.021605233, 0.05862753, -0.1281377, 0.033581465, 0.09292917, -0.009535642, 0.00008080082, -0.04046313, 0.032381173, 0.054466523, -0.08402035, -0.0031190887, -0.065295815, 0.08300677, 0.014016728, 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0.04651793, -0.0031674337, 0.045317642, -0.011902883, 0.08434042, -0.0029207072, -0.050412208, -0.023178946, 0.042677, -0.026393058, 0.026699798, 0.008882151, 0.1039185, 0.0036842255, -0.061668266, -0.040436458, 0.00900218, -0.042036846, -0.008415371, 0.022952225, -0.04659795, -0.015777154, -0.04651793, -0.03968961, -0.04675799, -0.014150093, 0.0051945914, 0.02095174, 0.0024806007, 0.03539524, 0.021365173, 0.0014645213, 0.057293873, -0.02249878, -0.027793396, -0.10007757, 0.04145004, 0.013056495, 0.024232535, -0.017230839, 0.015937192, -0.028940342, 0.06188165, -0.033741504, -0.09335594, -0.042036846, 0.026153, -0.0817798, -0.0017904335, 0.07820561, 0.04080988, -0.029473804, 0.06716293, 0.02645974, -0.04120998, -0.008655429, 0.049852073, 0.027793396, -0.026753144, -0.0012719746, 0.025966289, -0.024379237, 0.07628514, -0.08247331, 0.010295827, -0.012976476, 0.01587051, 0.0080019375, 0.020378267, 0.048865166, -0.007941923, -0.0039909664, -0.3230649, -0.024245871, -0.057507258, 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-0.09234236, -0.047798242, 0.018124389, 0.080606185, 0.00024380905, 0.059160993, -0.020978414, -0.037822492, -0.016537338, 0.028166821, -0.023805765, 0.031020846, 0.03683559, 0.028433552, -0.0043077096, 0.02393913, -0.07057709, -0.013129846, 0.016790733, -0.27996114, -0.009508969, 0.022378752, 0.01851115, -0.03011396, 0.019724777, 0.02285887, 0.0012836442, -0.016817406, 0.029900573, 0.014416824, 0.038169242, 0.05665372, 0.025406152, -0.004857843, -0.017217502, 0.0697769, -0.030167306, -0.04251696, 0.021631906, -0.031367596, -0.005708049, 0.14190103, -0.060868073, -0.02249878, 0.044917542, -0.028433552, 0.04686468, 0.036915608, 0.0056980466, 0.033554792, 0.02036493, -0.0023272303, -0.0359287, -0.01711081, 0.022845533, -0.0052179303, 0.04710474, 0.024512602, 0.05505333, -0.058947608, 0.049878746, -0.026673125, 0.0039476226, 0.06940348, -0.10066438, -0.031661, -0.022885542, -0.030220652, 0.04102327, -0.049958766, 0.0097890375, 0.06577593, 0.0026256358, 0.02747332, -0.06076138, 0.036302123, -0.017604263, 0.026739808, 0.009989086, -0.039556246, 0.057400566, -0.05246604, 0.12824439, -0.018324437 ]

Reassignment of the 92-kDa type IV collagenase gene (CLG4B) to human chromosome 20.

The collagenase type IV B gene (CLG4B) was previously mapped to human chromosome 16 by hybridization of a cDNA probe to DNAs from a somatic cell hybrid panel. We have relocalized CLG4B to chromosome 20 based on three different lines of evidence: screening a somatic cell hybrid mapping panel; fluorescence in situ hybridization (FISH); and linkage analysis using a newly identified polymorphism.

8978762

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Tandem 1;30 translocation: a new structural abnormality in the horse (Equus caballus).

A 1;30 tandem translocation was found in an 8-yr-old thoroughbred stallion referred because of reduced fertility. The diagnosis was confirmed by GTG and CBG staining. This is the first report of a tandem translocation in the horse.

8978763

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0.03829516, -0.053208698, 0.027615665, -0.03414202, 0.038591813, -0.025984075, 0.02315239, 0.038106382, -0.008468085, 0.10032253, 0.04751836 ]

The human HCLS1 gene maps to chromosome 3q13 by fluorescence in situ hybridization.

The human HS1 gene (HCLS1; hematopoietic cell-specific Lyn substrate 1) expressed in human hematopoietic cells encodes a major substrate of protein-tyrosine kinase; p75HS1. This intracellular protein is involved in the signal transduction pathways that initiate at the antigen receptors of both B and T lymphocytes. Fluorescence in situ hybridization using a 2.0-kb cDNA and an 8.0-kb genomic DNA clone of HCLS1 as probes revealed that the gene maps to 3q13.

8978766

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