bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotensin‐Metabolizing Peptidases in Rat Fundus Plasma Membranes
Authors: Checler Frédéric , Barelli Hélène , Kwan Chiu‐Yin , Kitabgi Patrick , Vincent Jean‐Pierre 
Published: October 2006

AbstractThe mechanisms by which neurotensin (NT) was inactivated by rat fundus plasma membranes were characterized. Primary inactivating cleavages occurred at the Arg8‐Arg9, Pro10‐Tyr11, and Ile12‐Leu13 peptidyl bonds. Hydrolysis at the Arg8‐Arg9 bond was fully abolished by the use of N‐[1 (R,S)‐carboxy‐2‐phenylethyl]‐alanyl‐alanyl‐phenylalanine‐p‐aminobenzoate, a result indicating the involvement at this site of a recently purified soluble metallopeptidase. Hydrolysis of the Pro10‐Tyr11 bond was totally resistant to N‐benzyloxycarbonyl‐prolyl‐prolinal and thiorphan, an observation suggesting that the peptidase responsible for this cleavage was different from proline endopeptidase and endopeptidase 24.11 and might correspond to a NT‐degrading neutral metallopeptidase recently isolated from rat brain synaptic membranes. The enzyme acting at the Ile12‐Leu13 bond has not yet been identified. Secondary cleavages occurring on NT degradation products were mainly generated by bestatin‐sensitive aminopeptidases and post‐proline dipeptidyl aminopeptidase. The content in NT‐metabolizing peptidases present in rat fundus plasma membranes is compared with that previously established for purified rat brain synaptic membranes.
Effects of Reserpine and Tetrabenazine on Catecholamine and ATP Storage in Cultured Bovine Adrenal Medullary Chromaffin Cells
Authors: Caughey Byron , Kirshner Norman 
Published: October 2006

AbstractThe in vivo storage relationship between catechol‐amines and ATP in chromaffin vesicles of cultured bovine adrenal medulla cells was investigated using drugs that block vesicular catecholamine uptake. Three‐day treatments with reserpine and tetrabenazine causing 85–90% depletion of catecholamines resulted in 41–46% reductions in cellular ATP content. Subcellular fractionation of reserpine‐treated cells indicated that the ATP is lost from the chromaffin vesicle pool. This was confirmed in experiments using metabolic inhibitors to differentiate the vesicular and extravesicular ATP pools. The vesicular ATP loss was not proportional to that of catecholamines, resulting in a reduction by 50% in the chromaffin vesicle mole ratio of catecholamines to ATP after 48 h of treatment. In metabolic labeling studies, it was found that reserpine treatment reduced the incorporation of [3H]adenosine into vesicular ATP selectively, but it reduced the incorporation of 32Pi into both the vesicular and extravesicular pools. The reduction of the [3H]adenosine incorporation was not due to diminished vesicular nucleotide uptake resulting from low catecholamine levels, because when the catecholamines were depleted by tetrabenazine pretreatment followed by removal of the drug before labeling, no reduction in [3H]adenosine incorporation was observed. When present during the labeling, tetrabenazine was found to be a reversible inhibitor of plasma membrane adenosine uptake. The observed loss of adenine nucleotides from catecholamine‐depleted chromaffin vesicles in vivo provides evidence that interactions between ATP and catecholamines are important in the vesicular storage of high concentrations of these compounds.
Myelin‐Associated Glycoprotein in the Central and Peripheral Nervous System of Quaking Mice
Authors: Inuzuka Takashi , Johnson David , Quarles Richard H. 
Published: October 2006

AbstractThe myelin‐associated glycoprotein (MAG) was quantitated in the CNS and PNS of quaking mice and the levels compared to the levels of myelin basic protein (MBP) and 2′:3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) activity. In the brainstems of 36‐day‐old quaking mice, MBP, MAG, and CNPase were reduced to 12, 16, and 29% of control levels, respectively. In the sciatic nerves of the 36‐day‐old quaking mice, MBP and CNPase were 38 and 75% of control levels, respectively, whereas the concentration of MAG was unchanged or slightly increased. Similar quantitative results were obtained for the sciatic nerves and spinal roots of 7‐month‐old quaking mice. Immunoblots showed that the principal MAG band from the brainstems, sciatic nerves, and spinal roots of the quaking mice had a higher than normal apparent Mr. In addition, there was a minor component reacting with anti‐MAG antiserum in the brain‐stems of the quaking mice that had a slightly lower Mr than control MAG and was not detected in the normal mice. The results for the quaking mice are compared with those from similar studies on other mutants with dysmyelination of the CNS and PNS.
Effect of Quinolinic Acid in the Nucleus Basalis Magnocellularis on Cortical High‐Affinity Choline Uptake
Authors: Metcalf R. H. , Boegman R. J. , Quirion R. , Riopelle R. J. , Ludwin S. K. 
Published: October 2006

AbstractA transient 45% increase in cortical high‐affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific (3H]hemicholinium‐3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.
Subcellular Distribution of Mammalian Tachykinins in Rat Basal Ganglia
Authors: Diez‐Guerra F. Javier , Richardson Peter J. , Emson Piers C. 
Published: October 2006

AbstractA combined differential and density gradient centrifugation procedure was used to study the subcellular localisation of the mammalian tachykinins in rat caudateputamen and substantia nigra. Substance P, neurokinin A, neuropeptide K, and neurokinin B were found to be concentrated in the synaptosomal fractions and in fractions containing heavy synaptic vesicles in both regions studied. In contrast, the catecholamines dopamine and noradrenaline had a more widespread distribution throughout the gradient. HPLC analysis of the immunoreactivity recovered showed that the tachykinin immunoreactivity coeluted with the relevant synthetic tachykinins, except in the soluble gradient fraction where neurokinin A immunoreactivity eluted in position consistent with neurokinin A3_10. These results suggest that, in the basal ganglia, the mammalian tachykinins are localised in fractions containing large dense cored synaptic vesicles. This vesicular localisation would be consistent with the proposed role of the tachykinins as neurotransmitters and neuromodulators.
Desensitization of Muscarinic Receptor‐Coupled Phosphoinositide Hydrolysis in Rat Hippocampus: Comparisons with the α1‐Adrenergic Response
Authors: Lenox Robert H. , Hendley Daniel , Ellis John 
Published: October 2006

AbstractIn the presence of lithium, carbamylcholine chloride (carbachol) and epinephrine increase the accumulation of inositol monophosphate severalfold in hippocampal slices from the rat. The stimulation by carbachol (EC50, 31 μM) is mediated by muscarinic receptors, whereas the effects of epinephrine (EC50, 2 μM) are due to activation of α1‐adrenergic receptors. The responses of epinephrine and carbachol are additive, even under conditions that significantly reduce the levels of phosphoinositides and free inositol, suggesting that the muscarinic and adrenergic receptors may be located on separate cells. At concentrations that saturate their respective receptors, epinephrine induces an increase in inositol monophosphate that is linear with time to at least 60 min, whereas the response to carbachol begins to reach a plateau by 20–40 min. When hippocampal slices are preincubated with saturating concentrations of carbachol, the subsequent response to carbachol is reduced by 42%. However, preincubation with carbachol or epinephrine has no effect on the subsequent response to epinephrine. Despite the lack of adrenergic desensitization by this paradigm, preexposure of hippocampal slices to the tumor‐promoting phorbol ester, phorbol 12,13‐dibutyrate, reduces the response to epinephrine to a significantly greater degree (57%) than it reduces the muscarinic response (25%). These studies indicate that, although they utilize the same second messenger, the muscarinic and α1‐adrenergic receptors of hippocampal slices have different characteristics and regulatory mechanisms.
N6‐Cyclohexyladenosine Inhibits Veratridine‐Stimulated Na Uptake by Rat Brain Synaptosomes
Authors: Simoes A. P. , Oliveira P. C. , Sebastião A. M. , Ribeiro J. A. 
Published: October 2006

AbstractThe effect of the stable adenosine analogue, N6‐cyclohexyladenosine, on 22Na uptake by rat brain synaptosomes stimulated by veratridine was investigated. In the presence of N6‐cyclohexyladenosine, both the initial rate and the maximum sodium uptake were decreased. The inhibitory effect of N6‐cyclohexyladenosine on sodium uptake by synaptosomes after 5 s of incubation with 22Na was concentration‐dependent, antagonized by 1,3‐dipropyl‐8‐p‐sulfophenylxanthine, and attenuated by increasing the concentration of veratridine. The possibility that the adenosine analogue, by activating a xanthine‐sensitive adenosine receptor, can operate inhibition of the voltage‐dependent sodium channels is discussed.
Sialyllactotetraosylceramide, a Ganglioside Marker for Human Malignant Gliomas
Authors: Fredman Pam , Hoist Hans von , Collins V. Peter , Granholm Lars , Svennerholm Lars 
Published: October 2006

AbstractThe ganglioside composition of surgically removed human glioma tissue was shown to differ from that of normal adult brain tissue. First, it contained reduced amounts of the major normal brain gangliosides of the gangliotetraose series. Second, it contained increased proportions of gangliosides not detected in normal brain tissue. One of these was isolated and established as being sialyllactotetraosylceramide 3′‐isoLM1. Radioimmunoassay for this ganglioside antigen in human glioma tissue revealed that 14/14 specimens of grades III and IV were positive but only 1/4 of grade II. Normal brain tissue was negative. These results suggest that sialyllactotetraosylceramide is a marker for human malignant gliomas.
Inhibition by Forskolin of Excitatory Amino Acid‐Induced Accumulation of Cyclic AMP in Guinea Pig Hippocampal Slices
Authors: Baba Akemichi , Nishiuchi Yukiko , Uemura Atsuhiro , Tatsuno Tohru , Iwata Heitaroh 
Published: October 2006

AbstractThe effect of forskolin on the excitatory amino acid‐induced accumulation of cyclic AMP was examined in hippocampal preparations of the guinea pig. Forskolin at concentrations of 0.1–10 μM remarkably enhanced the stimulatory effects of histamine and adenosine, whereas it markedly attenuated the stimulation induced by cysteine sulfinate, an excitatory amino acid. Forskolin reduced the maximal response to cysteine sulfinate without affecting the apparent ED50. At a concentration of 1 μM, forskolin also inhibited the stimulatory effects of glutamate, N‐methyl‐dl‐aspartate, and veratridine without affecting those of kainate and quisqualate. Pretreatment of the slices with 0.1 mM N‐ethylmaleimide partially prevented the attenuation by forskolin of cysteine sulfinate‐induced accumulation of cyclic AMP without affecting the stimulation induced by cysteine sulfinate. Forskolin at concentrations of < 1 μM did not affect GTP‐stimulated activity and Cl−‐dependent activity of adenylate cyclase of the hippocampal membranes.
Phosphatidylinositol Metabolism During In Vitro Hypoxia
Authors: Huang Hsueh‐Meei , Gibson Gary E. 
Published: October 2006

Abstract: The effects of in vitro histotoxic hypoxia (0.5 mM KCN) on potassium‐stimulated phosphatidylinositol turnover were determined. In rat cortical slices that were prelabeled with [2‐3H]inositol, depolarization with 60 mMKCl increased [2‐3H]inositol monophosphate and [2‐3H]inositol bisphosphate accumulation in a Ca2+‐dependent manner. At early times (10 s and 1 min), histotoxic hypoxia enhanced potassium‐stimulated [2‐3H]inositol bisphosphate formation. More prolonged hypoxia (10 and 30 min) reduced potassium‐stimulated [2‐3H]inositol monophosphate and inositol bisphosphate accumulation. Under basal conditions, hypoxia did not alter the accumulation of [2‐3H]inositol phosphates.These results are consistent with the following hypothesis. The hypoxic‐induced increase in cytosolic free calcium that we reported previously may lead to the early stimulation of inositol phosphates formation during hypoxia through activation of phospholipase C. The impairment of inositol phosphates formation during more prolonged hypoxia may be due to negative feedback regulation of the phosphatidylinositol cascade by protein kinase C or to a reduction in ATP levels.
tele‐Methylhistamine Levels and Histamine Turnover in Nuclei of the Rat Hypothalamus and Amygdala
Authors: Itoh Yoshinori , Oishi Ryozo , Nishibori Masahiro , Saeki Kiyomi 
Published: October 2006

AbstractAn HPLC method using fluorescence detection for the determination of tele‐methylhistamine! (t‐MH) was improved to a sensitivity level which enabled the detection of 0.05 pmol of tissue t‐MH. The t‐MH contents and the histamine turnover rates in various nuclei of the rat hypothalamus and amygdala were subsequently measured. The histamine turnover rates were estimated from pargyline‐induced t‐MH accumulation. Both the t‐MH levels and the histamine turnover rates were shown to be relatively high in the nuclei dorsomedialis and premammillaris ventralis of the hypothalamus, and also in the nucleus medialis of the amygdala. The steady‐state t‐MH levels in various nuclei of the hypothalamus and amygdala correlated well with the histamine turnover rates in these nuclei.
Glutamine and Aspartate Loading of Synaptosomes: A Reevaluation of Effects on Calcium‐Dependent Excitatory Amino Acid Release
Authors: McMahon Harvey T. , Nicholls David G. 
Published: October 2006

Abstract:Guinea‐pig cerebral cortical synaptosomes were preincubated for 60 min with 100 μMd‐aspartate, l‐aspartate, or l‐glutamate. The total d‐ plus l‐aspartate content of the synaptosomal fraction increased to 235%, 195%, or 164%, respectively, of the control. Despite this no increase was seen in the very low KCl evoked, Ca2+‐dependent release of aspartate. Preincubation with the three amino acids changed the synaptosomal glutamate content to 78% (d‐aspartate), 149% (l‐aspartate), or 168% (l‐glutamate) of control. However there was no statistically significant effect of these preincubations on the extent of Ca2+‐dependent glutamate release. Thus the Ca2+‐dependent release of aspartate and glutamate is not determined by the total synaptosomal content of these amino acids. The addition of 0.1–0.5 mM glutamine to the incubation caused a massive appearance of glutamate in the extrasynaptosomal medium. Analysis of specific activities showed that glutamine was hydrolysed directly by an extra‐synaptosomal glutaminase, and that intrasynaptosomal glutamate was predominantly labelled by uptake of this glutaminase‐derived glutamate. No increase was seen in the extent of Ca2+‐dependent release of glutamate (by fluorimetry) either after preincubation with glutamine or in the continued presence of glutamine. Thus we are unable to confirm reports that glutamine expands the transmitter pool of glutamate. The extrasynaptosomal glutaminase activity in the synaptosomal preparation was inhibited by Ca2+ and activated by phosphate. Identical kinetics were obtained with “free'’brain mitochondria, confirming the origin of the glutamine‐derived glutamate.
Human Neuroectoderm‐Derived Cell Line Secretes Fibronectin that Shares the HNK‐1/10C5 Carbohydrate Epitope with Neural Cell Adhesion Molecules
Authors: Harper John R. , Perry Susan K. , Davis Roxanne M. , Laufer David M. 
Published: October 2006

Abstract:A human malignant melanoma cell line, Melur, secretes several glycoproteins that contain a unique carbohydrate epitope shared by neural cell adhesion molecules and recognized by the monoclonal antibodies HNK‐1, L2, and 10C5. In this report, we present evidence that one of the major melanoma glycoproteins containing the HNK‐1/10C5 epitope is the cell adhesion molecule, fibronectin, or a fibronectin‐like molecule. Melanoma‐derived fibronectin was isolated from serum‐free conditioned medium by gelatin‐Sepharose affinity adsorption and shown to react with monoclonal antibodies HNK‐1 and 10C5 in Western blot analysis. HNK‐1‐containing fibronectin was purified on a gelatin‐Sepharose column followed by an affinity column using a monoclonal antibody against the HNK‐1 carbohydrate. The purified HNK‐1‐fibronectin then could be incorporated into the extracellular matrix of hamster fibroblasts in vitro, and such a matrix was detectable using the HNK‐1 monoclonal antibody in an immunofluorescence assay. Of the seven neuroectoderm‐derived tumor cell lines tested, only the Melur melanoma cell secreted fibronectin containing the HNK‐1 carbohydrate. Identification of human neuroectoderm‐derived fibronectin as a potential carrier of the HNK‐1 carbohydrate suggests a new role for fibronectin in neural development and regeneration, and represents a new model for studying the function of this carbohydrate domain in neural cell adhesion.
Multiple Pathways of N‐Kinase Activation in PC12 Cells
Authors: Rowland‐Gagné Elizabeth , Greene Lloyd A. 
Published: October 2006

Abstract:Past work established a cell‐free assay for a nerve growth factor (NGF)‐activated protein kinase activity (designated N‐kinase) that utilizes tyrosine hydroxylase and histone H1 as substrates and that is distinct from a variety of well‐characterized kinases. This study explores the specificity and mechanistic pathway(s) by which N‐kinase activity is regulated in PC12 rat pheochromocytoma cells. N‐kinase is rapidly activated in these cells by treatment with NGF, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), phorbol ester, or dibutyryl cyclic AMP. Our data indicate that the stimulated activity is the same for each agent by several criteria: It exhibits the same characteristic biphasic elution pattern by Mono S fast protein liquid chromatography (FPLC), except for the case of dibutyryl cyclic AMP in which one of the activity peaks is somewhat shifted; it shows the same elution pattern by FPLC on a Superose 12 column; it possesses identical substrate specificity; and, except in the case of dibutyryl cyclic AMP, it does not show additivity when each agent is added simultaneously with NGF. The multiple forms of N‐kinase are interconvertible in that rechromatography on a Mono S column yields a single peak of activity. Also, when NGF and dibutyryl cyclic AMP are simultaneously presented to cells, the chromatographic profile resembles that with NGF alone. Activation occurs through several independent initial pathways. Down‐regulation of protein kinase C by phorbol ester pretreatment prevents N‐kinase activation by phorbol ester, but not by the other agents. A PC12 cell‐derived line deficient in cyclic AMP‐dependent protein kinase II activity exhibits N‐kinase activation by all treatments except dibutyryl cyclic AMP. The properties of N‐kinase suggests that it is similar or identical to the ribosomal S6 protein kinase described by Blenis and Erikson. Additional experiments revealed that N‐kinase activity can be stimulated in several cell lines in addition to PC12 cells. These findings indicate that the N‐kinase can be activated via multiple second‐messenger pathways and that it could therefore potentially play a significant role in mediating shared intracellular responses to various extracellular signals.
Regional Difference in Responsiveness of Norepinephrine‐Sensitive Cyclic AMP‐Generating Systems of Rat Cerebral Cortex with Iron‐Induced Epileptic Activity
Authors: Hattori Yukio , Moriwaki Akiyoshi , Hayashi Yasushi , Hori Yasuo 
Published: October 2006

Abstract:Responsiveness of norepinephrine (NE)–sensitive cyclic AMP (cAMP)‐generating systems was determined in slices from different areas of the rat cerebral cortex in which FeCl2 solution was injected unilaterally into the sensorimotor cortex to induce epileptic activity. In anterior cortical areas of rats in which the appearance of electrographic isolated spikes was dominant either ipsilaterally or contralaterally to the injection site 8–10 days after the injection, the cAMP accumulations elicited by NE and an NE‐phentolamine combination were greater on the side of dominant spike activity than on the other. In anterior cortical areas of rats showing dominant spike activity on either side of the cortex 31–60 days after the injection, the cAMP accumulation elicited by NE was smaller on the dominant side than on the other. In anterior cortical areas of rats showing nearly equal spike activity on the two sides 31–60 days after the injection, the cAMP accumulations elicited by NE and an NE‐phentolamine combination were greater on the side ipsilateral to the injection site than on the other. In anterior and posterior cortical areas of rats in which the appearance of spike and wave complexes, as well as isolated spikes, was detected 31–60 days after the injection, the cAMP accumulations elicited by NE and combinations of NE and phentolamine or propranolol were greater on the side ipsilateral to the injection site than on the other. The elicitation by an NE‐propranolol combination, but not by an NE‐phentolamine combination, of cAMP accumulation was almost completely inhibited by 8‐phenyltheophylline. These results suggest that alterations in NE‐sensitive cAMP‐generating systems of the cortex involving α‐ and β‐adrenoceptors and adenosine receptors are related to the neurochemical process of iron‐induced epilepsy.
μ‐Opioid Receptors and Not K‐Opioid Receptors Are Coupled to the Adenylate Cyclase in the Cerebellum
Authors: Polastron J. , Boyer M.‐J. , Quertermont Y. , Thouvenot J.‐P. , Meunier J.‐C. , Jauzac Ph. 
Published: October 2006

Abstract:The putative regulatory effect of opioids on adenylate cyclase was investigated in two different preparations containing, respectively, two different populations of opioid receptors: the rabbit cerebellum (>75%μ‐opioid receptors) and the guinea pig cerebellum (>80%K‐opioid receptors). In the μ‐preparation, but not in the K‐preparation, opioids inhibited the basal and the forskolin‐stimulated adenylate cyclase activity in a dose‐dependent manner and stereospecifically. The inhibition was in the 20–30% range, required the presence in the assay medium of Mg2+ and of GTP, but was independent of the presence of Na+. Pharmacological characterization of the inhibitory response in the rabbit cerebellum clearly showed that it was under the control of a μ‐opioid binding site, with the effect being elicited by nonselective (etorphine and morphine) and μ‐selective (Tyr‐D‐Ala‐Gly‐Me‐Phe‐Gly‐ol) agonists, whereas δ‐ and K‐selective agonists were almost totally ineffective. ADP ribosylation of inhibitory GTP‐binding protein by pertussis toxin failed to block the inhibitory effect of opioids, and data presented suggest that this failure is likely to be the consequence of a limited access of the toxin to its substrate in rabbit cerebellum membranes.