abdelmo/pubmed-dataset · Datasets at Hugging Face

Guide RNA-directed uridine insertion RNA editing in vitro.

Guide RNAs (gRNAs) have been proposed to mediate uridine (U) addition/deletion editing of mitochondrial mRNAs in kinetoplastid protozoa. The Us are proposed to be derived either from UTP by two successive cleavage-ligations or transesterifications; or from the 3' end of the gRNA by the same mechanisms. We have demonstrated gRNA-dependent U insertions into a specific editing site of a pre-edited mRNA which was incubated in a mitochondrial extract from Leishmania tarentolae. The predominant number of U insert

8978701

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Guide RNA-directed uridine insertion RNA editing in vitro.

ions was determined by the number of guiding nucleotides in the added gRNA; and the formation of a gRNA-mRNA anchor duplex was necessary for activity. UTP and alpha-beta bond hydrolysis of ATP were required; and the activity was inhibited above 50-100 mM KCl. A gRNA-independent insertion of up to approximately 13 Us occurred in the absence of the added cognate gRNA; the extent of this activity was affected by sequences upstream and downstream of the edited region. Heparin inhibited the gRNA-independent U in

8978701

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Guide RNA-directed uridine insertion RNA editing in vitro.

sertion activity and had no effect on the gRNA-dependent activity. Blocking the 3' OH of the gRNA had little effect on the gRNA-dependent U insertion activity. The data are consistent with a cleavage-ligation model in which the Us are derived directly from UTP.

8978701

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Antagonistic actions of activin A and BMP-2/4 control dorsal lip-specific activation of the early response gene XFD-1' in Xenopus laevis embryos.

Transcription of the early response gene XFD-1' (XFKH1) in the dorsal lip (Spemann organizer) of Xenopus embryos is activated by dorsal mesoderm inducing factors. Promoter studies revealed the presence of an activin A response element (ARE) which is both necessary and sufficient for transcriptional activation of reporter genes in animal cap explants incubated with activin A. Surprisingly; this ARE is also active within vegetal explants in the absence of exogenously added inducers; but an additional inhibito

8978699

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Antagonistic actions of activin A and BMP-2/4 control dorsal lip-specific activation of the early response gene XFD-1' in Xenopus laevis embryos.

ry response element prevents transcription of the XFD-1' gene in the ventral/vegetal region of the embryo in vivo. This element is located upstream of the ARE; it responds to bone morphogenic proteins 2 and 4 (BMP-2/4) triggered signals and it overrides the activating properties of the ARE. Expression patterns of BMP-2 and BMP-4 in the late blastula stage embryo and; especially; their absence from the dorsal blastopore lip may thus control the spatial transcription of the XFD-1' gene. Accordingly; the tempo

8978699

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Antagonistic actions of activin A and BMP-2/4 control dorsal lip-specific activation of the early response gene XFD-1' in Xenopus laevis embryos.

ral activation and the spatial restriction of XFD-1' gene activity to the Spemann organizer is regulated by antagonistic actions of two distinct members of the TGF-beta family (activin and BMP) which act on different promoter elements.

8978699

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Heat shock disassembles the nucleolus and inhibits nuclear protein import and poly(A)+ RNA export.

Heat shock causes major positive and negative changes in gene expression; drastically alters the appearance of the nucleolus and inhibits rRNA synthesis. We here show that it causes many yeast nucleolar proteins; including the fibrillarin homolog Nop1p; to relocate to the cytoplasm. Relocation depends on several proteins implicated in mRNA transport (Mtrps) and is reversible. Two observations indicate; surprisingly; that disassembly results from a reduction in Ssa protein (Hsp70) levels: (i) selective deple

8978700

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Heat shock disassembles the nucleolus and inhibits nuclear protein import and poly(A)+ RNA export.

tion of Ssa1p leads to disassembly of the nucleolus; (ii) preincubation at 37 degrees C protects the nucleolus against disassembly by heat shock; unless expression of Ssa proteins is specifically inhibited. We observed that heat shock or reduction of Ssa1p levels inhibits protein import into the nucleus and therefore we propose that inhibition of import leads to disassembly of the nucleolus. These observations provide a simple explanation of the effects of heat shock on the anatomy of the nucleolus and rRNA

8978700

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Heat shock disassembles the nucleolus and inhibits nuclear protein import and poly(A)+ RNA export.

transcription. They also extend understanding of the path of nuclear export. Since a number of nucleoplasmic proteins also relocate upon heat shock; these observations can provide a general mechanism for regulation of gene expression. Relocation of the hnRNP-like protein Mtr13p (= Npl3p; Nop3p); explains the heat shock sensitivity of export of average poly(A)+ RNA. Strikingly; Hsp mRNA export appears not to be affected.

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The G222D mutation in elongation factor Tu inhibits the codon-induced conformational changes leading to GTPase activation on the ribosome.

Elongation factor Tu (EF-Tu) from Escherichia coli carrying the mutation G222D is unable to hydrolyze GTP on the ribosome and to sustain polypeptide synthesis at near physiological Mg2+ concentration; although the interactions with guanine nucleotides and aminoacyl-tRNA are not changed significantly. GTPase and polypeptide synthesis activities are restored by increasing the Mg2+ concentration. Here we report a pre-steady-state kinetic study of the binding of the ternary complexes of wild-type and mutant EF-

8978702

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The G222D mutation in elongation factor Tu inhibits the codon-induced conformational changes leading to GTPase activation on the ribosome.

Tu with Phe-tRNA(Phe) and GTP to the A site of poly(U)-programed ribosomes. The kinetic parameters of initial binding to the ribosome and subsequent codon-anticodon interaction are similar for mutant and wild-type EF-Tu; independent of the Mg2+ concentration; suggesting that the initial interaction with the ribosome is not affected by the mutation. Codon recognition following initial binding is also not affected by the mutation. The main effect of the G222D mutation is the inhibition; at low Mg2+ concentrat

8978702

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The G222D mutation in elongation factor Tu inhibits the codon-induced conformational changes leading to GTPase activation on the ribosome.

ion; of codon-induced structural transitions of the tRNA and; in particular; their transmission to EF-Tu that precedes GTP hydrolysis and the subsequent steps of A-site binding. Increasing the Mg2+ concentration to 10 mM restores the complete reaction sequence of A-site binding at close to wild-type rates. The inhibition of the structural transitions is probably due to the interference of the negative charge introduced by the mutation with negative charges either of the 3' terminus of the tRNA; bound in the

8978702

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The G222D mutation in elongation factor Tu inhibits the codon-induced conformational changes leading to GTPase activation on the ribosome.

vicinity of the mutated amino acid in domain 2 of EF-Tu; or of the ribosome. Increasing the Mg2+ concentration appears to overcome the inhibition by screening the negative charges.

8978702

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Two intracellular signaling pathways for the dopamine D3 receptor: opposite and synergistic interactions with cyclic AMP.

As cerebral neurons express the dopamine D1 receptor positively coupled with adenylyl cyclase; together with the D3 receptor; we have investigated in a heterologous cell expression system the relationships of cyclic AMP with D3 receptor signaling pathways. In NG108-15 cells transfected with the human D3 receptor cDNA; dopamine; quinpirole; and other dopamine receptor agonists inhibited cyclic AMP accumulation induced by forskolin. Quinpirole also increased mitogenesis; assessed by measuring [3H]thymidine in

8978703

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Two intracellular signaling pathways for the dopamine D3 receptor: opposite and synergistic interactions with cyclic AMP.

corporation. This effect was blocked partially by genistein; a tyrosine kinase inhibitor. Forskolin enhanced by 50-75% the quinpirole-induced [3H]thymidine incorporation. This effect was maximal with 100 nM forskolin; occurred after 6-16 h; was reproduced by cyclic AMP-permeable analogues; and was blocked by a protein kinase A inhibitor. Forskolin increased D3 receptor expression up to 135%; but only after 16 h and at concentrations of > 1 microM. Thus; in this cell line; the D3 receptor uses two distinct s

8978703

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Two intracellular signaling pathways for the dopamine D3 receptor: opposite and synergistic interactions with cyclic AMP.

ignaling pathways: it efficiently inhibits adenylyl cyclase and induces mitogenesis; an effect possibly involving tyrosine phosphorylation. Activation of the cyclic AMP cascade potentiates the D3 receptor-mediated mitogenic response; through phosphorylation by a cyclic AMP-dependent kinase of a yet unidentified component. Hence; transduction of the D3 receptor can involve both opposite and synergistic interactions with cyclic AMP.

8978703

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Insulin promotes the hydrolysis of a glycosyl phosphatidylinositol in cultured rat astroglial cells.

Glycosyl phosphatidylinositols have been implicated in insulin signaling through their action as precursors of second messenger molecules in peripheral tissues. In the present study; cultured rat astrocytes were used to investigate whether glycosyl phosphatidylinositol might be involved in the mechanism of insulin signal transduction in neural cells. A glycosyl phosphatidylinositol sensitive to hydrolysis by both phosphatidylinositol-specific phospholipase C and glycosyl phosphatidylinositol-specific phosph

8978704

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Insulin promotes the hydrolysis of a glycosyl phosphatidylinositol in cultured rat astroglial cells.

olipase D and to nitrous acid deamination was purified. When astrocytes were exposed to 10 nM insulin; a rapid and significant reduction in the content of glycosyl phosphatidylinositol was observed within 1-2 min. In addition; an inverse concentration-dependent relationship between glycosyl phosphatidylinositol and diacylglycerol levels was found; suggesting a phospholipase C-mediated hydrolysis of glycosyl phosphatidylinositol in response to insulin. The effects of insulin were mediated through its own rec

8978704

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Insulin promotes the hydrolysis of a glycosyl phosphatidylinositol in cultured rat astroglial cells.

eptors and not through insulin-like growth factor (IGF)-I and/or IGF-II receptors; as demonstrated by affinity cross-linking studies. Also; the effects of 5 nM IGF-1 or 5 nM IGF-II on glycosyl phosphatidylinositol and diacylglycerol levels were different from those caused by insulin and were not essentially modified by pretreatment of the cells with either platelet-derived growth factor (PDGF) or epidermal growth factor (EGF). When cells were sequentially incubated with PDGF and EGF; a reduction in both gly

8978704

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Insulin promotes the hydrolysis of a glycosyl phosphatidylinositol in cultured rat astroglial cells.

cosyl phosphatidylinositol and diacylglycerol contents was observed; the diacylglycerol but not the glycosyl phosphatidyl content was reversed after incubation with IGF-I; and especially with IGF-II; for 10 min. Despite the remarkable homology among insulin; IGF-I; and IGF-II; our results indicate that in astrocytes these compounds probably use different signal transduction pathways.

8978704

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Retinoic acid is a negative regulator of the neuropeptide Y/peptide YY Y1 receptor gene in SK-N-MC cells.

To identify effectors of neuropeptide Y Y1 receptor gene expression predicted by putative regulatory elements in its 5' flanking region; we examined the effects of several transcriptionally active agents on Y1 receptor mRNA levels and 125I-peptide YY binding capacity in SK-N-MC cells. Phorbol ester caused a rapid; transient 2.6-fold increase in Y1R mRNA levels. However; all trans-retinoic acid caused a rapid; sustained decrease in Y1 receptor mRNA levels (to 25% of control). Cycloheximide pretreatment did n

8978705

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Retinoic acid is a negative regulator of the neuropeptide Y/peptide YY Y1 receptor gene in SK-N-MC cells.

ot attenuate the maximal inhibitory effect of retinoic acid; but it prolonged the time to achieve maximal efficacy. The retinoic acid effect was secondary to both a significant decrease in Y1 receptor mRNA stability and a decreased Y1 receptor gene transcription rate. Y1 receptor binding capacity was also significantly decreased after retinoic acid treatment (368 +/- 25 vs. 496 +/- 28 fmol/mg of protein for control). These data support a role for retinoic acid as an important agent regulating Y1 receptor ge

8978705

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Retinoic acid is a negative regulator of the neuropeptide Y/peptide YY Y1 receptor gene in SK-N-MC cells.

ne expression and mediating Y1 receptor down-regulation.

8978705

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Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity.

Pigment epithelium-derived factor (PEDF) is a survival factor for cerebellar granule cells in culture. In the present study; we have investigated the ability of a recombinant form of PEDF (rPEDF) to protect against glutamate neurotoxicity. When rPEDF was added to cerebellar granule cell cultures 30 min before addition of 100 microM glutamate; glutamate-induced neuronal death was significantly reduced. The protective effect of rPEDF was dose-dependent in the range from 0.023 to 7.0 nM (1-500 ng/ml); with a h

8978706

[ null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null ]

Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity.

alf-maximal dose of 0.47 nM. An antibody to rPEDF blocked this protective effect. Measurement of intraneuronal free calcium levels demonstrated that rPEDF raised the basal calcium content. However; after the elevation of intracellular calcium in response to administration of glutamate; rPEDF reduced the plateau level seen in the presence of glutamate. These data show that PEDF can protect neurons against glutamate-induced neurotoxicity; possibly via a calcium-related pathway. The finding that only 30 min of

8978706

[ null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null ]

Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity.

preincubation is required for the neuroprotective effect; significantly faster than other known neurotrophic factors; suggests that PEDF may be useful clinically as a neuroprotective agent in the CNS.

8978706

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L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro.

L-Deprenyl is a relatively selective inhibitor of monoamine oxidase (MAO)-B that delays the emergence of disability and the progression of signs and symptoms of Parkinson's disease. Experimentally; deprenyl has also been shown to prevent neuronal cell death in various models through a mechanism that is independent of MAO-B inhibition. We examined the effect of deprenyl on cultured mesencephalic dopamine neurons subjected to daily changes of feeding medium; an experimental paradigm that causes neuronal death

8978707

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L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro.

associated with activation of the NMDA subtype of glutamate receptors. Both deprenyl (0.5-50 microM) and the NMDA receptor blocker MK-801 (10 microM) protected dopamine neurons from damage caused by medium changes. The nonselective MAO inhibitor pargyline (0.5-50 microM) was not protective; indicating that protection by deprenyl was not due to MAO inhibition. Deprenyl (50 microM) also protected dopamine neurons from delayed neurotoxicity caused by exposure to NMDA. Because deprenyl had no inhibitory effect

8978707

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L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro.

on NMDA receptor binding; it is likely that deprenyl protects from events occurring downstream from activation of glutamate receptors. As excitotoxic injury has been implicated in neurodegeneration; it is possible that deprenyl exerts its beneficial effects in Parkinson's disease by suppressing excitotoxic damage.

8978707

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Effect of continuous phorbol ester treatment on muscarinic receptor-mediated calmodulin redistribution in SK-N-SH neuroblastoma cells.

Stimulation of muscarinic receptors by carbachol and activation of protein kinase C elicits the translocation of calmodulin (CaM) from membranes to cytosol in the human neuroblastoma cell line SK-N-SH. Our previous studies have suggested a role for protein kinase C in the regulation of CaM redistribution. To explore further the role of protein kinase C in carbachol-induced calmodulin translocation; we treated cells for 17 h with 12-O-tetradecanoylphorbol 13-acetate (TPA) to down-regulate protein kinase C is

8978708

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Effect of continuous phorbol ester treatment on muscarinic receptor-mediated calmodulin redistribution in SK-N-SH neuroblastoma cells.

ozymes or 72 h to differentiate the cells. Treatment of SK-N-SH cells for 17 h with 70 nM TPA nearly abolished the effect of carbachol on CaM redistribution. After 72 h of TPA; however; the cells appeared differentiated; and the ability of carbachol to increase cytosolic CaM levels was restored. In untreated control cells; the carbachol-mediated increase in cytosolic CaM content was mimicked by TPA and blocked by pretreatment with the selective protein kinase C inhibitor Ro 31-8220 at 10 microM. In the 72-h

8978708

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Effect of continuous phorbol ester treatment on muscarinic receptor-mediated calmodulin redistribution in SK-N-SH neuroblastoma cells.

TPA-treated cells; however; the ability of TPA to increase cytosolic CaM levels was significantly reduced; and the action of carbachol was no longer blocked by Ro 31-8220. The effect of prolonged TPA treatment on select protein kinase C isozymes was examined by immunoblotting. Treatment of cells for either 17 or 72 h abolished the alpha-isozyme in the cytosol and reduced (17 h) or abolished (72 h) the content in the membranes. In both 17- and 72-h TPA-treated cells; the epsilon-isozyme was nearly abolished

8978708

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Effect of continuous phorbol ester treatment on muscarinic receptor-mediated calmodulin redistribution in SK-N-SH neuroblastoma cells.

in the cytosol and slightly reduced in the membranes. Some protein kinase C activity may have been maintained during TPA treatment because the basal level of phosphorylation of the protein kinase C substrate myristoylated alanine-rich C kinase substrate was enhanced in cells treated for either 17 or 72 h with TPA. The potential dissociation of carbachol and protein kinase C in eliciting increases in cytosolic CaM content was a function of prolonged TPA treatment and not differentiation per se because carba

8978708

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Effect of continuous phorbol ester treatment on muscarinic receptor-mediated calmodulin redistribution in SK-N-SH neuroblastoma cells.

chol-mediated increases in cytosolic CaM levels were inhibited by Ro 31-8220 in retinoic acid-differentiated SK-N-SH cells. This study demonstrates that continuous TPA treatment; although initially down-regulating the protein kinase C-mediated effect of carbachol on CaM redistribution; uncouples carbachol and protein kinase C at longer times.

8978708

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Regulation of alpha 2A-adrenergic receptor mRNA in rat astroglial cultures: role of cyclic AMP and protein kinase C.

In this study we investigated regulation of alpha 2A-adrenergic receptor (alpha 2A-AR) mRNA in rat astroglial cultures by increases in intracellular cyclic AMP levels and by protein kinase C (PKC) activation. Treatment of astroglial cultures with forskolin (FSK); an adenylyl cyclase activator; or with the membrane-permeable cyclic AMP analogues dibutyryl cyclic AMP or Sp-adenosine 3';5'-cyclic monophosphothioate triethylamine caused time- and concentration-dependent decreases in the levels of a approximatel

8978709

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Regulation of alpha 2A-adrenergic receptor mRNA in rat astroglial cultures: role of cyclic AMP and protein kinase C.

y 4.0-kb alpha 2A-AR mRNA transcript. Levels of alpha 2A-AR mRNA were reduced to approximately 10% of control levels within 4 h of 1 microM FSK treatment. PKC agonists [phorbol 12-myristate 13-acetate (PMA); phorbol 12;13-dibutyrate; and mezerein] also decreased alpha 2A-AR mRNA levels in a time- and concentration-dependent fashion. A 90% decrease in alpha 2A-AR mRNA levels was observed with 50 nM PMA in 4 h. The decrease in alpha 2A-AR mRNA levels caused by FSK and PMA treatment appears to be the result of

8978709

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Regulation of alpha 2A-adrenergic receptor mRNA in rat astroglial cultures: role of cyclic AMP and protein kinase C.

decreases in transcription of the alpha 2A-AR gene and is not due to decreases in alpha 2A-AR mRNA degradation rate. These observations suggest that alpha 2A-AR mRNA levels are regulated by cyclic AMP and PKC.

8978709

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Neurotrophin protection against toxicity induced by low potassium and nitroprusside in cultured cerebellar granule neurons.

Long-term survival of cultured rat cerebellar granule neurons requires depolarizing concentrations of potassium (high potassium; 25 mM KCl). A high-potassium culturing condition has been reported to increase the intracellular calcium concentration ([Ca2+]i) and the expression of brain-derived neurotrophic factor (BDNF); which in turn induces the expression of neurotrophin-3 (NT-3) in these neurons. We therefore examined the neurotrophic effect of these two neurotrophins in low-potassium (5 mM) cultures and

8978711

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Neurotrophin protection against toxicity induced by low potassium and nitroprusside in cultured cerebellar granule neurons.

their neuroprotective capabilities against sodium nitroprusside-induced neurotoxicity in both low- and high-potassium cultures. Neuronal survival and neurotrophic effects were monitored by [3H]ouabain binding and 3-(4;5-dimethylthiazol-2-yl)-2;5-diphenyltetrazolium bromide assays. In low-potassium cultures; the neurotrophic effect of BDNF approached that found in high-potassium cultures but was much more robust than that of NT-3. In contrast; undifferentiated neurons cultured in high-potassium medium were m

8978711

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Neurotrophin protection against toxicity induced by low potassium and nitroprusside in cultured cerebellar granule neurons.

uch less responsive to BDNF and not responsive at all to NT-3. Induction of nitroprusside neurotoxicity occurred more readily in low- than in high-potassium cultures. BDNF; NT-3; and a high potassium concentration; alone or in combination; were unable to protect neurons treated with nitroprusside at 50 or 100 microM. However; the neurotoxicity of a lower dose of nitroprusside (10 microM) was reversed by the combined actions of these two neurotrophins in low-potassium cultures and by BDNF alone in high-potas

8978711

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Neurotrophin protection against toxicity induced by low potassium and nitroprusside in cultured cerebellar granule neurons.

sium cultures. Because nitroprusside neurotoxicity is less robust in high-potassium cultures; high-potassium-induced BDNF expression and subsequent NT-3 expression may participate in its neuroprotection and neurotrophism in these cultures. Also; we found that toxic doses of nitroprusside antagonized KCl- and NMDA-induced rises in [Ca2+]i; suggesting that this effect is related to nitroprusside-induced neurotoxicity.

8978711

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Transgenic murine dopaminergic neurons expressing human Cu/Zn superoxide dismutase exhibit increased density in culture, but no resistance to methylphenylpyridinium-induced degeneration.

Primary dopaminergic neuronal cultures with increased superoxide dismutase (SOD) activity were established for studying the role of superoxide anion (O2-) in 1-methyl-4-phenylpyridinium (MPP+)-induced degeneration of dopamine (DA) neurons. Mean SOD activity in cultures prepared from transgenic (human) Cu/Zn SOD (hSOD1) mice was 2.46-2.60 times greater than in cultures prepared from nontransgenic control mice. After 1 and 2 weeks in culture; the mean density of DA neurons [number of tyrosine hydroxylase-immu

8978710

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Transgenic murine dopaminergic neurons expressing human Cu/Zn superoxide dismutase exhibit increased density in culture, but no resistance to methylphenylpyridinium-induced degeneration.

noreactive (TH-ir) cells per visual field] was significantly higher in cultures prepared from transgenic mice compared with those prepared from nontransgenic control mice (4.55-5.63 TH-ir neurons per field in hSOD1 cultures vs. 2.66-2.8 TH-ir neurons per field in control cultures). However; uptake of [3H]DA relative to uptake of [3H]GABA was only slightly greater in hSOD1 cultures than in normal cultures (14.1 nmol of DA/100 nmol of GABA vs. 12.1 nmol of DA/100 nmol of GABA). Resistance to MPP+ toxicity was

8978710

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Transgenic murine dopaminergic neurons expressing human Cu/Zn superoxide dismutase exhibit increased density in culture, but no resistance to methylphenylpyridinium-induced degeneration.

not significantly different from that in normal cultures when based on density of surviving TH-ir cell bodies (EC50 = 0.54 microM in hSOD1 and EC50 = 0.37 microM in normal cultures). A more sensitive measure of DA neuron integrity and function ([3H]DA uptake) also failed to demonstrate increased resistance of hSOD1 cultures to the toxin (EC50 = 73.7 nM in hSOD1 and EC50 = 86.2 nM in controls). These results do not support the hypothesis that neurotoxicity of the active metabolite of MPTP; MPP+; is mediated

8978710

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Transgenic murine dopaminergic neurons expressing human Cu/Zn superoxide dismutase exhibit increased density in culture, but no resistance to methylphenylpyridinium-induced degeneration.

by generation of O2- in the cytoplasm. Nevertheless; mesencephalic cultures with increased hSOD1 activity appear to survive better than normal control cultures in the oxidatively stressful environment of cell culture incubators; and such mesencephalic cells may be useful for cell grafting studies in animal models of Parkinson's disease.

8978710

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Endothelin stimulates phospholipase D in striatal astrocytes.

In primary cultures of mouse striatal astrocytes prelabeled with [3H]myristic acid; endothelin (ET)-1 induced a time-dependent formation of [3H]phosphatidic acid and [3H]diacylglycerol. In the presence of ethanol; a production of [3H]phosphatidylethanol was observed; indicating the activation of a phospholipase D (PLD). ET-1 and ET-3 were equipotent in stimulating PLD activity (EC50 = 2-5 nM). Pretreatment of the cells with pertussis toxin partially abolished the effect of ET-1; indicating the involvement o

8978712

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Endothelin stimulates phospholipase D in striatal astrocytes.

f a Gi/G(o) protein. Inhibition of protein kinase C by Ro 31-8220 or down-regulation of the kinase by a long-time treatment with phorbol 12-myristate 13-acetate (PMA) totally abolished the ET-1-induced stimulation of PLD. In contrast; a cyclic AMP-dependent process is not involved in the activation of PLD; because the ET-1-evoked formation of [3H]phosphatidylethanol was not affected when cells were coincubated with either isoproterenol; 8-bromo-cyclic AMP; or forskolin. Acute treatment with PMA also stimula

8978712

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Endothelin stimulates phospholipase D in striatal astrocytes.

ted PLD through a protein kinase C-dependent process. However; the ET-1 and PMA responses were additive. Furthermore; the ET-1-evoked response; contrary to that of PMA; totally dependent on the presence of extracellular calcium. These results suggest that at least two distinct mechanisms are involved in the control of PLD activity in striatal astrocytes. Finally; ET-1; ET-3; and PMA also stimulated PLD in astrocytes from the mesencephalon; the cerebral cortex; and the hippocampus.

8978712

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K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR.

K-252b potentiates the neurotrophic effects of neurotrophin-3 (NT-3) in primary cultures of rat central cholinergic and peripheral sensory neurons and in a rat pheochromocytoma PC12 cell line. The ligand and receptor specificity; and role of the low-affinity neurotrophin receptor (p75NTR) in the potentiation response induced by K-252b; are unknown. To address the issues of ligand and receptor specificity of K-252b potentiation; we have examined neurotrophin-induced DNA synthesis ([3H]-thymidine incorporatio

8978713

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K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR.

n) in NIH3T3 cells expressing trkA; trkB; or trkC. Neither NT-3 nor K-252b alone could stimulate mitogenic activity in the trkA-overexpressing clone. However; coaddition of K-252b (EC50 of approximately 2 nM) with 10-100 ng/ml NT-3 led to incorporation of [3H]thymidine in trkA expressing cells to a level induced by optimal concentrations of nerve growth factor (NGF). The K-252b- and NT-3-induced [3H]thymidine incorporation correlated with an increase in the tyrosine autophosphorylation of the trkA receptor

8978713

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K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR.

as well as tyrosine phosphorylation of trk-associated phospholipase C-gamma 1 and SH2-containing proteins. K-252b did not potentiate submaximal doses of NGF; or maximal doses of brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/ 5) in trkA-expressing cells. Furthermore; K-252b did not potentiate DNA synthesis by submaximal doses of BDNF; NT-4/5; or NT-3 in trkB- or trkC-expressing NIH3T3 cells; suggesting that the potentiation profile for K-252b was specific for NT-3 in trkA-expressing cell

8978713

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K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR.

s. We found no expression of p75NTR in the trk-expressing NIH3T3 cells. This is the first demonstration that K-252b potentiates a trkA-mediated biological nonneuronal response by NT-3 that occurs independent of p75NTR and appears to be both ligand and receptor specific.

8978713

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Okadaic acid induces hyperphosphorylation of tau independently of mitogen-activated protein kinase activation.

Hyperphosphorylation of the microtubule-associated protein tau is a characteristic of Alzheimer brain tissue. Recent in vitro data suggest that mitogen-activated protein kinase (MAPK); a proline-directed protein kinase; phosphorylates the sites on tau common to Alzheimer's disease. Using an okadaic acid-induced tau hyperphosphorylation model; we have tested the requirement for MAPK activity; using a specific inhibitor ¿PD098059 [2-(2'-amino-3'-methoxyphenyl)oxanaphthalen-4-one]¿ of the MAPK activator Mek1.

8978715

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Okadaic acid induces hyperphosphorylation of tau independently of mitogen-activated protein kinase activation.

Mobility shift; phosphoepitope analysis; and direct measurement of kinase activity indicated that the Mek1 inhibitor dose-dependently blocked basal and okadaic acid-induced MAPK activation. Despite a block of MAPK activation by this inhibitor; robust tau hyperphosphorylation was observed in response to okadaic acid. In addition; activation of MAPK by phorbol 12-myristate 13-acetate did not result in tau phosphorylation; indicating that in primary cultures of cortical neurons elevated MAPK activity is not su

8978715

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Okadaic acid induces hyperphosphorylation of tau independently of mitogen-activated protein kinase activation.

fficient to induce tau hyperphosphorylation.

8978715

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Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.

Nitric oxide has been recognized in recent years as an important mediator of neuronal toxicity; which in many cases involves alterations of the cytoplasmic Ca2+ concentration ([Ca2+]i). In [Ca2+]i fluorimetric experiments on cultured hippocampal neurons; the nitric oxide-releasing agent S-nitrosocysteine produced a delayed rise in [Ca2+]i over a 20-min exposure; which was accompanied by a progressive slowing of the kinetics of recovery from depolarization-induced [Ca2+]i transients. These effects were block

8978714

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Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.

ed by oxyhemoglobin and by superoxide dismutase; confirming nitric oxide as the responsible agent; and suggesting that they involved peroxynitrite formation. Similar alterations of [Ca2+]i homeostasis were produced by the mitochondrial ATP synthase inhibitor oligomycin; and when an ATP-regenerating system was supplied via the patch pipette in combined whole-cell patch-clamp-[Ca2+]i fluorimetry experiments; S-nitrosocysteine had no effect on the resting [Ca2+]i or on the recovery kinetics of [Ca2+]i transien

8978714

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Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.

ts induced by direct depolarization. We conclude that prolonged exposure to nitric oxide disrupts [Ca2+]i homeostasis in hippocampal neurons by impairing Ca2+ removal from the cytoplasm; possibly as a result of ATP depletion. The resulting persistent alterations in [Ca2+]i may contribute to the delayed neurotoxicity of nitric oxide.

8978714

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Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in cultured rat cortical neurons.

Primary embryonic cortical cultures were used as an in vitro model to evaluate the influence of glia on developmental expression of alpha 7-type nicotinic acetylcholine receptors in rat brain. In cells cultured in serum-containing medium without mitotic inhibitors; specific 125I-alpha-bungarotoxin binding to alpha 7-type nicotinic receptors was maximal 4-8 days after plating. Treatment with 5'-fluorodeoxyuridine (80 microM) from 1 to 3 days in vitro significantly reduced glial proliferation and concomitantl

8978716

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Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in cultured rat cortical neurons.

y increased 125I-alpha-bungarotoxin binding; whereas plating onto a glial bed layer decreased binding. There was no significant binding to pure glial cultures. Treatment-induced changes in neuronal binding resulted from alterations in receptor density; with no change in affinity. 5'-Fluorodeoxyuridine treatment also increased cellular expression of alpha 7 receptor mRNA but had no effect on N-[3H]methylscopolamine binding to muscarinic receptors. Glial conditioned medium decreased 125I-alpha-bungarotoxin bi

8978716

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Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in cultured rat cortical neurons.

nding in both control and 5'-fluorodeoxyuridine-treated cultures; suggesting the release of a soluble factor that inhibits alpha 7-type nicotinic receptor expression. An additional mechanism of glial regulation may involve removal of glutamate from the surrounding medium; as added glutamate (200 microM) increased 125I-alpha-bungarotoxin binding in astrocyte-poor cultures but not in those that were astrocyte enriched. These results suggest that glia may serve a physiological role in regulating alpha 7-type n

8978716

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Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in cultured rat cortical neurons.

icotinic receptors in developing brain.

8978716

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Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus.

Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABAA receptors throughout the CNS. Conceivably; changes in receptor function may be associated with alterations of subunit composition. In the present study; a comprehensive (1-12 weeks) ethanol treatment paradigm was used to evaluate changes in GABAA receptor subunit expression in several brain regions including the cerebel

8978717

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Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus.

lum; cerebral cortex; ventral tegmental area (VTA) (a region implicated in drug reward/dependence); and the hippocampus (a region involved in memory/cognition). Expression of alpha 1 and alpha 5 subunits was regulated by ethanol in a region-specific and time-dependent manner. Following 2-4 weeks of administration; cortical and cerebellar alpha 1 and alpha 5 subunits immunoreactivity was reduced. In the VTA; levels of alpha 1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1-4 we

8978717

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Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus.

eks of treatment. Hippocampal alpha 1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast; alpha 5 mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABAA receptor subunit expression in the VTA and hippocampus; effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol.

8978717

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5-Hydroxytryptamine-facilitated release of substance P from rat spinal cord slices is mediated by nitric oxide and cyclic GMP.

The role of nitric oxide (NO) in the control of 5-hydroxytryptamine (5-HT)-induced release of substance P was investigated in rat spinal cord in vitro. 5-HT facilitated the 60 mM K(+)-evoked release of substance P-like immunoreactive materials (SPLI) from the superfused rat dorsal spinal cord slices without affecting spontaneous SPLI release. The facilitatory effect of 5-HT was significantly inhibited by ICS 205-930 or granisetron (potent and specific 5-HT3 receptor antagonists); by NG-monomethyl-L-arginine

8978718

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5-Hydroxytryptamine-facilitated release of substance P from rat spinal cord slices is mediated by nitric oxide and cyclic GMP.

(NMMA; a NO synthase inhibitor); and by methylene blue or 1H-[1;2;4] oxadiazolo [4;3-a] quinoxaline-1-one (MB or ODQ; respectively; both are inhibitors of soluble guanylyl cyclase) and was mimicked by 2-methylserotonin (2-m-5-HT; a selective 5-HT3 receptor agonist); L-arginine (a precursor of NO); or 8-bromo-cyclic GMP. NMMA; MB; or ODQ inhibited the 2-m-5-HT-induced increase of cyclic GMP levels in the rat dorsal spinal cord slices. These data suggest that the facilitatory effect of 5-HT on the release of

8978718

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5-Hydroxytryptamine-facilitated release of substance P from rat spinal cord slices is mediated by nitric oxide and cyclic GMP.

SPLI is mediated by the 5-HT3 receptor and that the intracellular signaling is mediated via NO by an increase in cyclic GMP production.

8978718

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Inhibitors of histamine methylation in brain promote formation of imidazoleacetic acid, which interacts with GABA receptors.

In brain; the precursor of imidazoleacetic acid (IAA); a GABAA agonist but a GABAC antagonist; is not known. In the periphery; IAA derives from oxidation of histamine. But in brain; histamine is thought to be metabolized solely by histamine methyltransferase (HMT); forming tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA). We showed that [3H]-histamine (intracerebroventricularly) could be converted to IAA in brains of rats; a process increased by inhibition of HMT. This demonstrated t

8978720

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Inhibitors of histamine methylation in brain promote formation of imidazoleacetic acid, which interacts with GABA receptors.

hat brain can oxidize histamine and suggested that endogenous histamine might also be oxidized if HMT activity were reduced. We examined in rat cerebral cortex; effects of the following HMT inhibitors (mg/kg i.p.): metoprine (10); tacrine (10); velnacrine (10; 30); and physostigmine (1;2). Tacrine was a potent inhibitor (Ki approximately 22 nM). To measure histamine in tissue that contained HMT inhibitors; we developed a gas chromatography-mass spectrometry method. After 2 h; all drugs reduced endogenous le

8978720

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Inhibitors of histamine methylation in brain promote formation of imidazoleacetic acid, which interacts with GABA receptors.

vels of t-MH and t-MIAA and increased levels of histamine and IAA. Our results show that inhibition of HMT promotes oxidation of histamine in brain; probably by shunting histamine to an alternative metabolic pathway. Formation of IAA provides a novel interaction between histaminergic and GABAergic systems in brain. Accumulation of IAA should be considered when inhibitors of HMT are used to probe brain histamine function.

8978720

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Down-regulation of norepinephrine transporters on PC12 cells by transporter inhibitors.

To investigate the regulation of norepinephrine transporters (NETs) in vitro; we measured the binding of the NET-selective ligand [3H]nisoxetine in homogenates of PC12 cells after exposure of intact cells to the NET inhibitor desipramine (DMI). A 3-day exposure of PC12 cells to DMI robustly reduced the Bmax; but not the KD; of [3H]nisoxetine binding to NETs. Reduction of the binding of [3H]nisoxetine was dependent on both the concentration of DMI and the time of exposure to DMI. Reduction of [3H]nisoxetine

8978719

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Down-regulation of norepinephrine transporters on PC12 cells by transporter inhibitors.

binding to NETs produced by a 1-day exposure to DMI reverted to preexposure levels 48 h after cessation of DMI exposure. Similar down-regulation of NETs was found when PC12 cells were exposed to another NET-selective drug; nisoxetine; which is structurally unrelated to DMI. In contrast; exposure of cells to the serotonin transporter-selective drug citalopram; or the NET substrate norepinephrine; had no effects on the binding of [3H]nisoxetine to NETs. The down-regulation of NETs was paralleled by a DMI-indu

8978719

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Down-regulation of norepinephrine transporters on PC12 cells by transporter inhibitors.

ced reduction in the uptake of [3H]norepinephrine in intact PC12 cells. It can be inferred from these data that inhibitors of the NET can down-regulate NETs directly; and do so in the absence of changes in the synaptic concentration of norepinephrine.

8978719

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Real-time measurement of electrically evoked extracellular dopamine in the striatum of freely moving rats.

The real-time measurement of electrically evoked dopamine was established in brain extracellular fluid of freely moving rats. Dopamine was monitored by fast-scan cyclic voltammetry at carbon fiber microelectrodes lowered into the striatum by means of a detachable micromanipulator. A stimulating electrode; previously implanted in the substantia nigra; was used to evoke striatal dopamine efflux. Evoked extracellular dopamine was both current and frequency dependent. When low current intensities (+/-125 microA

8978721

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Real-time measurement of electrically evoked extracellular dopamine in the striatum of freely moving rats.

) and frequencies (10-20 Hz) were applied; detectable levels of dopamine were elicited without a perceptible behavioral response. Reproducible concentrations of extracellular dopamine could be evoked in the same rat for at least 2 months. These concentrations; moreover; were significantly higher in freely moving rats compared with rats anesthetized with Equithesin. Analysis of measured curves for dopamine uptake and release rates revealed that anesthesia inhibits release but does not affect uptake. It is co

8978721

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Real-time measurement of electrically evoked extracellular dopamine in the striatum of freely moving rats.

ncluded that (a) fast-scan cyclic voltammetry at carbon fiber microelectrodes is a viable technique for the measurement of electrically evoked dopamine in brain extracellular fluid of freely moving rats; (b) it is possible to determine in situ rate constants for dopamine release and uptake from these temporally and spatially resolved measurements of levels of dopamine; and (c) transient changes in extracellular dopamine levels elicited by electrical stimulation are affected by anesthesia.

8978721

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Dual modulation of dopamine release from anterior nucleus accumbens through cholecystokinin-B receptor subsites.

Previous binding studies have suggested the existence of two affinity states for cholecystokinin-B (CCK-B) receptor. One study; using BC 197 and BC 264; two highly selective CCK-B agonists; has shown that BC 197 is selective for one subsite; B1; and that BC 264 has the same affinity for the two subsites; B1 and B2. Therefore; the possible involvement of CCK-B subsites in the modulation of endogenous dopamine (DA) release from slices of the anterior part of the nucleus accumbens was investigated with these t

8978722

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Dual modulation of dopamine release from anterior nucleus accumbens through cholecystokinin-B receptor subsites.

wo agonists in order to associate a functional response with activation of each subsite. The selective B1 agonist BC 197 produced a dose-dependent increase of 35 mM K(+)-stimulated DA release. In contrast; at a low concentration (20 nM); BC 264 inhibited the K(+)-evoked DA release; whereas at a higher concentration (1 microM); it stimulated the DA release. These two opposing effects were suppressed by the CCK-B antagonist PD-134;308; but not by the CCK-A antagonist L-364;718 and were not prevented by tetrod

8978722

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Dual modulation of dopamine release from anterior nucleus accumbens through cholecystokinin-B receptor subsites.

otoxin; a Na(+)-channel blocker. Moreover; BC 264 at 20 nM; in the presence of PD-134;308 at a concentration that would block the B2 subsites (0.1 nM); increased the evoked DA release. All together; these results support further the existence of distinct CCK-B subsites and suggest that; in the anterior nucleus accumbens; their stimulation mediates opposite effects on K(+)-stimulated DA release via a presynaptic mechanism.

8978722

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Calcium/calmodulin-dependent kinase II phosphorylates Drosophila visual arrestin.

Light activation of rhodopsin in the Drosophila photoreceptor induces a G protein-coupled signaling cascade that results in the influx of Ca2+ into the photoreceptor cells. Immediately following light activation; phosphorylation of a photoreceptor-specific protein; phosrestin I; is detected. Strong sequence similarity to mammalian arrestin and electroretinograms of phosrestin mutants suggest that phosrestin I is involved in light inactivation. We are interested in identifying the protein kinase responsible

8978723

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Calcium/calmodulin-dependent kinase II phosphorylates Drosophila visual arrestin.

for the phosphorylation of phosrestin I to link the transmembrane signaling to the light-adaptive response. Type II Ca2+/calmodulin-dependent kinase is one of the major classes of protein kinases that regulate cellular responses to transmembrane signals. We show here that partially purified phosrestin I kinase activity can be immunodepleted and immunodetected with antibodies to Ca2+/calmodulin-dependent kinase II and that the kinase activity exhibits regulatory properties that are unique to Ca2+/calmodulin-

8978723

[ null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null, null ]

Calcium/calmodulin-dependent kinase II phosphorylates Drosophila visual arrestin.

dependent kinase II such as Ca2+ independence after autophosphorylation and inhibition by synthetic peptides containing the Ca2+/calmodulin-dependent kinase II autoinhibitory domain. We also show that Ca2+/calmodulin-dependent kinase KII activity is present in Drosophila eye preparations. These results are consistent with our hypothesis that Ca2+/calmodulin-dependent kinase II phosphorylates phosrestin I. We suggest that Ca2+/calmodulin-dependent kinase II plays a regulatory role in Drosophila photoreceptor

8978723

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Calcium/calmodulin-dependent kinase II phosphorylates Drosophila visual arrestin.

light adaptation.

8978723

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Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission.

The mouse mutant coloboma (Cm/+); which exhibits profound spontaneous hyperactivity and bears a deletion mutation on chromosome 2; including the gene encoding synaptosomal protein SNAP-25; has been proposed to model aspects of attention-deficit hyperactivity disorder. Increasing evidence suggests a crucial role for SNAP-25 in the release of both classical neurotransmitters and neuropeptides. In the present study; we compared the release of specific neurotransmitters in vitro from synaptosomes and slices of

8978724

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Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission.

selected brain regions from Cm/+ mice with that of +/+ mice. The release of dopamine (DA) and serotonin (5-HT) from striatum; and of arginine vasopressin and corticotropin-releasing factor from hypothalamus and amygdala is calcium-dependent. Glutamate release from and content in cortical synaptosomes of Cm/+ mice are greatly reduced; which might contribute to the learning deficits in these mutants. In dorsal striatum of Cm/+ mutants; but not ventral striatum; KCl-induced release of DA is completely blocked

8978724

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Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission.

and that of 5-HT is significantly attenuated; suggesting that striatal DA and 5-HT deficiencies may be involved in hyperactivity. Further; although acetylcholine failed to induce hypothalamic corticotropin-releasing factor release from Cm/+ slices; restraint stress increased plasma corticosterone levels in Cm/+ mice to a significantly higher level than in +/+ mice; suggesting an important role for arginine vasopressin in hypothalamic-pituitary-adrenal axis activation. These results suggest that reduced SNAP

8978724

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Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission.

-25 expression may contribute to a region-specific and neurotransmitter-specific deficiency in neurotransmitter release.

8978724

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A novel regulation of expression of the alpha-subunit of the G stimulatory protein by dopamine via D1 dopamine receptors.

Exposure of human neuroblastoma SK-N-MC cells to 100 microM dopamine (DA) for 72 h caused 70% loss of immunodetectable membrane-bound levels of the alpha-subunit of Ga. The loss in Gs alpha was accompanied by reduced (64.3 +/- 0.35% of control values) NaF-mediated stimulation of adenylyl cyclase and was independent of accumulated cyclic AMP (cAMP) levels; because neither forskolin nor dibutyryl cAMP treatment of cells mimicked the DA-induced effects. The reduction in Gs alpha content was manifest at the tra

8978725

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A novel regulation of expression of the alpha-subunit of the G stimulatory protein by dopamine via D1 dopamine receptors.

nscriptional level; Gs alpha mRNA levels were attenuated to 56.5 +/- 10% of control values after a 24-h treatment of cells with 100 microM DA. The concentration of DA required to produce the half-maximal decrease of Gs alpha mRNA content was 20 nM; similar to the high-affinity binding value (8.5 nM) of DA to D1 sites. Gs alpha mRNA levels were also attenuated (52 +/- 3.5% of control values) by the D1-selective agonist SKF R-38393 but not by forskolin or dibutyryl cAMP. Attenuation of Gs alpha mRNA levels by

8978725

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A novel regulation of expression of the alpha-subunit of the G stimulatory protein by dopamine via D1 dopamine receptors.

agonists was blocked by the D1-selective antagonist SCH 23390. Stimulation of adenylyl cyclase-inhibitory DA receptors; which are coexpressed in these cells; failed to down-regulate Gs alpha mRNA; indicating that regulation of Gs alpha mRNA expression occurs specifically through chronic stimulation of D1 DA receptors.

8978725

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Serotonin stimulation of 5-HT4 receptors indirectly enhances in vivo dopamine release in the rat striatum.

Serotonin (5-HT) applied at 1; 3; and 10 microM into the striatum of halothane-anesthetized rats by in vivo microdialysis enhanced dopamine (DA) outflow up to 173; 283; and 584% of baseline values; respectively. The 5-HT effect was partially reduced by 1 or 10 microM GR 125;487; a 5-HT4 antagonist; and by 100 microM DAU 6285; a 5-HT3/4 antagonist; whereas the 5-HT1/2/6 antagonist methiothepin (50 microM) was ineffective. In the presence of tetrodotoxin the effect of 1 microM 5-HT was not affected by 5-HT4 a

8978726

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Serotonin stimulation of 5-HT4 receptors indirectly enhances in vivo dopamine release in the rat striatum.

ntagonists. In addition; tetrodotoxin abolished the increase in DA release induced by the 5-HT4 agonist (S)- zacopride (100 microM). In striatal synaptosomes; 1 and 10 microM 5-HT increased the outflow of newly synthesized [3H]DA up to 163 and 635% of control values; respectively. The 5-HT4 agonists BIMU 8 and (S)-zacopride (1 and 10 microM) failed to modify [3H]DA outflow; whereas 5- methoxytryptamine (5-MeOT) at 10 microM increased it (62%). In prelabeled [3H]DA synaptosomes; 1 microM 5-HT; but not (S)-za

8978726

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Serotonin stimulation of 5-HT4 receptors indirectly enhances in vivo dopamine release in the rat striatum.

copride (1 and 10 microM); increased [3H]DA outflow. DAU 6285 (10 microM) failed to modify the enhancement of newly synthesized [3H]DA outflow induced by 5-MeOT or 5-HT (1 microM); whereas the effect of 5-HT was reduced to the same extent by the DA reuptake inhibitor nomifensine (1 microM) alone or in the presence of DAU 6285. These results show that striatal 5-HT4 receptors are involved in the 5-HT-induced enhancement of striatal DA release in vivo and that they are not located on striatal DA terminals.

8978726

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Gene-based neurotransmitter modulation in cerebellar granule neurons.

The human glutamic acid decarboxylase (GAD) gene was transferred into rat cerebellar granule neurons. Following adenoviral-mediated gene transfer; nearly 100% of the neurons had transgene expression that persisted for the duration of their survival in culture. GABA levels were elevated both in the growth media and in lysates of GAD-modified granule neurons. In GAD-modified neurons; extracellular GABA levels steadily increased with time; whereas intracellular GABA levels peaked 10 days after gene transfer. G

8978727

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Gene-based neurotransmitter modulation in cerebellar granule neurons.

AD-modified neurons released both glutamate and GABA into the surrounding media before and after potassium-induced stimulation; but only the release of glutamate was sensitive to potassium stimulation. These data suggest that glutamatergic neurons; which initially contained no detectable GABA; can be genetically modified to release GABA constitutively.

8978727

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Avian melatonin synthesis: photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina.

The circadian rhythms in melatonin production in the chicken pineal gland and retina reflect changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase; AA-NAT; EC 2.3.1.87). Here we determined that the chicken AA-NAT mRNA is detectable in follicular pineal cells and retinal photoreceptors and that it exhibits a circadian rhythm; with peak levels at night. AA-NAT mRNA was not detected in other tissues. The AA-NAT mRNA rhythm in the pineal gland and retina persists in consta

8978728

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Avian melatonin synthesis: photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina.

nt darkness (DD) and constant lighting (LL). The amplitude of the pineal mRNA rhythm is not decreased in LL. Light appears to influence the phase of the clock driving the rhythm in pineal AA-NAT mRNA in two ways: The peak is delayed by approximately 6 h in LL; and it is advanced by > 4 h by a 6-h light pulse late in subjective night in DD. Nocturnal AA-NAT mRNA levels do not change during a 20-min exposure to light; whereas this treatment dramatically decreases AA-NAT activity. These observations suggest th

8978728

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Avian melatonin synthesis: photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina.

at the rhythmic changes in chicken pineal AA-NAT activity reflect; at least in part; clock-generated changes in mRNA levels. In contrast; changes in mRNA content are not involved in the rapid light-induced decrease in AA-NAT activity.

8978728

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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.

The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study; the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug L-DOPA were analyzed. By using in vivo microdialysis in the urethane-anesthetized rat; it was f

8978730

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