Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The C57BL/10 SPS/sps mouse mutant are audiogenic seizure-susceptible. The enzymatic activities of glutamate decarboxylase (GAD), GABA aminotransferase (GABA-T), alanine aminotransferase (ALA-T), aspartate aminotransferase (ASP-T), and glutamate dehydrogenase (GDH) of whole brain supernatant are significantly reduced in these epileptic mice. GABA uptake is decreased in cortex, midbrain, and pons medulla. Previous studies showed the presence of two sodium-dependent GLU uptake systems in normal (SPS/SP) mice. Glutamate Umax by System 1 is significantly decreased in these mice, whereas the Umax value for System 2 is significantly increased in the epileptic mice.
Mol Neurobiol
PMID:Altered GABAergic and glutamatergic transmission in audiogenic seizure-susceptible mice. 788 3

The cellular co-expression of adenosine A2a receptor mRNA and preproenkephalin A (PPE A) mRNA and A2a receptor mRNA and prosomatostatin (pSRIF) mRNA in rat striatum was studied using a combination of radioactive and non-radioactive in situ hybridization techniques. Cells containing adenosine A2a receptor mRNA were visualised using an 35S-labelled oligonucleotide whilst those containing PPE A mRNA and pSRIF mRNA were detected using alkaline phosphatase-labelled antisense oligonucleotides; both radioactive and non-radioactive hybridization signals were visualized on the same tissue section. Bright field examination of striatal sections hybridized with both the [35S]adenosine A2a receptor probe and the alkaline phosphatase-labelled PPE A probe revealed dense clusters of silver grains overlying cells containing alkaline phosphatase reaction product demonstrating that the two gene transcripts were expressed by the same medium-sized nerve cells. The cellular expression of the two mRNAs was consistently found to be concordant demonstrating that adenosine A2a receptor mRNA is expressed by medium-sized striatal enkephalin cells. In contrast, clusters of silver grains were never detected overlying striatal cells containing pSRIF mRNA indicating that this population of interneurones do not express the adenosine A2a receptor sub-type. The expression of adenosine A2a receptors by enkephalin cells in striatum suggests that adenosine may play a role in modulating the activity of GABA/enkephalin striatopallidal neurones through interaction with A2a receptors.
Brain Res Mol Brain Res 1994 Mar
PMID:Adenosine A2a receptor mRNA is expressed by enkephalin cells but not by somatostatin cells in rat striatum: a co-expression study. 791 1

The redistribution of glutamate and GABA in postischemic brains was examined immunocytochemically using the gerbil model of unilateral 1 h cerebral ischemia. In the cerebral neocortex, the majority of neurons underwent recovery processes after 5 h of recirculation, while neurons in the hippocampus were irreversibly damaged. Glutamate-like immunoreactivity (LI) was highly increased in the degenerating hippocampal CA3 pyramidal cells after recirculation, while in the neocortex and the hippocampal CA1 sector, the pyramidal cells showed only slightly increased glutamate-LI. GABA-LI-positive punctae in the neuropil, corresponding to neuronal processes of GABAergic neurons, were accentuated after recirculation both in the cerebral neocortex and the hippocampus. Although the astrocytes on the nonischemic side showed neither glutamate-LI nor GABA-LI, the swollen astrocytes and their foot processes, which were observed after recirculation, often showed strong glutamate-LI and GABA-LI. These data suggest (1) the accumulation of glutamate or glutamate-like substances, especially in the CA3 pyramidal cells, (2) the excitation of the GABAergic neurons and their subsequent uptake of GABA, and (3) the sequestration of the extracellular neurotransmitters by astrocytes in the postischemic period.
Mol Chem Neuropathol 1994 May
PMID:Redistribution of glutamate and GABA in the cerebral neocortex and hippocampus of the Mongolian gerbil after transient ischemia. An immunocytochemical study. 791 66

Prolonged benzodiazepine treatment of rats results in anticonvulsant tolerance in vivo. Studies of in vitro hippocampal slices following 1 wk flurazepam administration show reduced GABA-mediated inhibition in the CA1 region, and a decrease in GABAA agonist and benzodiazepine potency to inhibit CA1 pyramidal cell-evoked responses. To investigate the molecular basis of benzodiazepine tolerance in the hippocampus, in situ hybridization techniques were used to evaluate the expression of the mRNAs for the alpha 1, alpha 5, and gamma 2 subunits of the GABAA receptor in the hippocampal formation and frontal cortex of chronic flurazepam-treated rats. A discretely localized decrease in alpha 1, but not alpha 5 or gamma 2 mRNA expression was found in the CA1 region (35-40%) and in layers II-III and IV of cortex (50-60%) 2 d after cessation of flurazepam treatment. The decrease in the expression of alpha 1 subunit mRNA in cortex is similar to that reported following other chronic benzodiazepine treatment regimens. This is the first report of a reduction in alpha 1 subunit mRNA expression in the hippocampal formation.
J Mol Neurosci 1993
PMID:Expression of alpha 1, alpha 5, and gamma 2 GABAA receptor subunit mRNAs measured in situ in rat hippocampus and cortex following chronic flurazepam administration. 791 36

Chronic GABA exposure of mammalian primary cultured cortical neurons results in a downregulation of the GABA-benzodiazepine receptor complex. In the present study, the mRNA levels, as well as polypeptide expression, for the GABAA receptor alpha 2 and alpha 3 subunits in cultured embryonic mouse cerebral cortical neurons (7 day old) were examined using northern analysis and immunoblotting techniques following chronic GABA treatment. The alpha 1 subunit mRNA or polypeptide could not be detected in these neurons. The steady state levels of mRNA for the GABAA receptor alpha 2 and alpha 3 subunits showed a decrease in comparison with untreated neurons. There was no change in the level of the beta actin or poly(A)+ RNA under the same experimental conditions. This agonist-induced reduction in the GABAA receptor alpha 2 and alpha 3 subunit mRNA was blocked by the concomitant exposure of neurons to R 5135, an antagonist of GABAA receptor. The polypeptide expression for the GABAA receptor alpha 2 and alpha 3 subunits in chronically GABA-treated neurons also showed a decline and this change was also blocked by the concomitant exposure of cells to GABA and R 5135. These results indicate that the chronic exposure of the GABAA receptor complex to agonist downregulates the expression of the alpha subunits of the receptor complex, which may be related to an observed decreases in the number of binding sites and GABA-induced 36Cl-influx in the cortical neurons.
Brain Res Mol Brain Res 1994 Jul
PMID:Chronic GABA treatment downregulates the GABAA receptor alpha 2 and alpha 3 subunit mRNAS as well as polypeptide expression in primary cultured cerebral cortical neurons. 796 53

The effects of kainic acid (15 mg/kg i.p.) on alpha subunits of the Gs and Go protein mRNA levels in the rat hippocampal formation were investigated. An in situ hybridization study showed an increase in the Gs alpha mRNA level in the dentate gyrus at 3 h (by ca. 17%), 24 h (by ca. 75%), 72 h (by ca. 89%) and 30 days (by ca. 59%) after kainic acid administration. An emulsion autoradiography revealed enhancement in the Gs alpha mRNA signal intensity over granular cells of the dentate gyrus and over some hilar cells adjacent to the granule cell layer, most likely in GABA interneurons. The Gs alpha mRNA showed a slight tendency to increase in the CA1 and CA3 pyramidal cell layers at 3 h after kainic acid administration, but it decreased after 24 h, 72 h and 30 days. The latter decrease correlated well with the pyramidal cells loss in those areas. Kainic acid differently influenced the Go alpha mRNA level in the dentate gyrus: it had no effect after 3 h, while after 24 h the mRNA level tended to decrease (by ca. 16%); then it increased after 72 h (by ca. 20%) and, to a lesser extent, after 30 days (by ca. 12%). The Go alpha mRNA level in CA1 and CA3 tended to decrease at 3 h after kainic acid administration; the signal completely disappeared after 24, 72 h as well as after 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1994 Jul
PMID:Seizure-induced expression of G proteins in the rat hippocampus. 796 78

Progesterone elicits a rapid, transient calcium influx in sperm that is a prerequisite for the progesterone-induced acrosome reaction. The possibility that the GABAA receptor/chloride channel was the receptor that mediated the progesterone-induced calcium influx in human sperm was examined. A-ring reduced 3 alpha-hydroxy pregnane steroids (e.g. alfaxalone, allopregnanolone, pregnanolone), which are active on the GABAA receptor/chloride channel, were found to be much weaker than progesterone at stimulating Ca2+ influx in sperm. The effects of a variety of progesterone metabolites and analogs and other steroids were compared for their ability to (i) stimulate GABA-induced 36Cl- uptake in synaptoneurosomes, (ii) stimulate GABA-induced Cl- currents in HEK-293 cells transfected with alpha 1, beta 2, and gamma 2 subunits of the GABAA receptor/chloride complex, and (iii) elicit a rapid Ca2+ influx in sperm. No correlation was observed between the ability of a given steroid to stimulate Ca2+ influx and efficacy in eliciting either 36Cl- uptake or chloride currents. Importantly, the action of progesterone to stimulate Ca2+ influx was not modified by GABA, diazepam, picrotoxin and pentobarbitol (known regulators of the GABAA receptor/chloride channel). It is concluded from these studies that the cell surface progesterone binding site on human sperm that mediates progesterone-induced changes in [Ca2+]i is unlike the steroid binding site on the GABAA receptor/chloride channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Sep
PMID:The cell surface progesterone receptor which stimulates calcium influx in human sperm is unlike the A ring reduced steroid site on the GABAA receptor/chloride channel. 798 50

PC12 cells, in the presence of nerve growth factor (NGF), support replication of the mouse-derived scrapie strains 139A and ME7, with the former yielding 100-1000-fold higher levels of infectivity. Infectivity remained cell-associated and cells did not show any gross morphological alterations, although changes were observed by electron microscopy in the form of an increased number of lipid droplets in 139A-infected cultures. Analysis of phospholipid metabolism in 139A infected cells indicated that scrapie replication did not change the inositol phosphate levels, but did stimulate phosphoinositide synthesis. Replication was not detected in PC12 cells infected with either the hamster-derived 263K or rat-derived 139R scrapie strains. Since scrapie-infected cultures did not exhibit cell death or any gross changes, any scrapie-induced effects would probably be manifested in nonvital cellular functions. When compared to controls, infection with the 139A scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, as well as the GABA synthetic pathway; however, the adrenergic pathway was unaffected by scrapie infection. The effects of the 139A scrapie strain on the cholinergic system appeared to be dose-dependent and were first detected prior to the detection of scrapie agent replication in these cells. No neurotransmitter-related enzymatic changes were detected in 263K- or 139R-infected PC12 cells. The enzymatic changes observed in ME7-infected PC12 cells and in Chandler agent-infected mouse neuroblastoma cells suggest that the significant changes in neurotransmitter levels in cultures exhibiting low infectivity titers must involve factors other than, but not excluding, replication of the agent. The role of additional factors is also suggested in studies of protein kinase C activity in 139A- and 139R-infected PC12 cells. These studies emphasize the value of the PC12 cell model system in examining the scrapie strain-host cell interaction and, in addition, support the concept of variation among scrapie strains.
Mol Neurobiol
PMID:Scrapie strain infection in vitro induces changes in neuronal cells. 799 9

Messenger RNA (mRNA) for several subunits of the GABAA receptor was measured in the cortex of mice chemically kindled with FG 7142. At 10 days after the final FG 7142 injection, beta 2 and gamma 2S subunit mRNA were significantly increased. At 31 days, alpha 1, alpha 3, beta 2, and gamma 2L mRNA were elevated. In contrast, levels of mRNA for four subunits of the glutamate receptor in the cortex of FG 7142-kindled mice killed at 31 days were not significantly increased. Previous investigations have shown a reduction in GABA-gated chloride channel function and density in mice kindled with FG 7142, and the increases in subunit mRNA found in the present studies may be a response to these decreases. These results indicate that chemical kindling produces long-lasting changes in expression of genes coding for specific neurotransmitter receptor subunits.
Brain Res Mol Brain Res 1994 Mar
PMID:GABAA and glutamate receptor subunit mRNAs in cortex of mice chemically kindled with FG 7142. 801 88

In order to facilitate study of the neuronal GABA transporter and provide a convenient system for potential drug screening, we have established a CHO cell line, designated 1F9, which stably expresses the cloned GABA transporter from rat brain (GAT-1). 1F9 cells transport GABA at levels approximately 300-fold higher than untransfected CHO cells, and GABA transport in these cells has the following properties: (1) a dependence on sodium and chloride ions; (2) higher sensitivity to neuronal subtype uptake inhibitors (DABA and ACHC) than to glial subtype inhibitors (beta-alanine and THPO); and (3) Km (2.5 microM) and IC50 values for various competitive ligands that are comparable with values determined in synaptosomes and brain slices. Given the fidelity with which the 1F9 cell line expresses these characteristics of the native neuronal GABA transporter, we have used it to further address GABA transporter activity. [3H]GABA uptake by 1F9 cells is inhibited approximately 50% by the chloride transport blockers DIDS and SITS. The GABA receptor agonists muscimol and baclofen also inhibit GABA transport; however, the receptor antagonists bicuculline and phaclofen have no effect. 1F9 cells also show release of [3H]GABA release is calcium independent, and is differentially affected by changes in the ion gradient, as well as by the presence of external substrates and uptake blockers. These experiments indicate that 1F9 cells provide a convenient system for the screening of GABA transport inhibitors.
Mol Membr Biol
PMID:GABA uptake and release by a mammalian cell line stably expressing a cloned rat brain GABA transporter. 801 97


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