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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of baclofen and GABA on rat piriform cortex neurons were investigated electrophysiologically using a brain slice preparation. 2. At resting potential GABA depolarized and baclofen hyperpolarized the cell, probably through activation of Cl and K conductances acting at GABAA and GABAB receptors, respectively. 3. The GABAA receptors were concentrated on the apical and basal dendrites near the cell body, while the baclofen-sensitive GABA receptors were concentrated particularly on the basal dendrites. 4. The different distributions of receptor localization must have functional consequences which remain to be elucidated.
Cell Mol Neurobiol 1990 Dec
PMID:Differential effects of baclofen and gamma-aminobutyric acid (GABA) on rat piriform cortex pyramidal neurons in vitro. 196 26

In mammalian brain, the activation of GABAA-receptors is associated with the opening of chloride channels, whose function can be allosterically modulated by drugs, in particular by ligands of the benzodiazepine receptor. Agonistic ligands potentiate while inverse agonists reduce the efficiency of GABA. We have cloned cDNAs encoding alpha 1- and beta 1-subunits of the GABAA-receptor from rat brain. When the corresponding RNAs were co-expressed in Xenopus oocytes. GABA-induced currents were recorded which were inhibited by bicuculline and potentiated by pentobarbital. GABA activated the channel in a weakly cooperative manner. Furthermore, the GABA-response was modulated by benzodiazepine receptor ligands. However, not only various agonists but also the antagonist flumazenil and the inverse agonist DMCM potentiated the GABA-response. Thus, alpha 1- and beta 1-subunits are sufficient to form GABAA-receptors which contain benzodiazepine binding sites, although in a functionally restricted form.
Brain Res Mol Brain Res 1990 Aug
PMID:GABAA-receptor expressed from rat brain alpha- and beta-subunit cDNAs displays potentiation by benzodiazepine receptor ligands. 197 69

Plasma membrane potential generated by Na+, K(+)-ATPase provides the driving force for high-affinity, Na(+)-dependent uptake of glutamate into the cytoplasm of glutamatergic nerve endings and glial cells. Ca2(+)-calmodulin-dependent ATPase in the plasma membrane and Ca2(+)-ATPase in the endoplasmic reticulum influence the intracellular [Ca2+] and, therefore, the exocytotic release of neurotransmitter glutamate. The membrane potential across the membrane of the synaptic vesicles, generated by a H(+)-ATPase, provides the driving force for synaptic vesicular uptake of glutamate as well as that of GABA and glycine. Hypoxia and ischemia lead to release of glutamate, perhaps in consequence of an increased endogenous pool of glutamate and/or lack of substrate (ATP) for the ATPases. This release, rather than being exocytotic, is believed to result mainly from a reversal of the Na(+)-dependent high-affinity glutamate transporter in the plasma membrane.
Mol Chem Neuropathol 1990 Jan
PMID:Interrelationship between glutamate and membrane-bound ATPases in nerve cells. 198 May 85

Functional interactions between steroidal anesthetics and gamma-aminobutyric acidA (GABAA) receptors have been examined with 36Cl- uptake measurements in rat cerebrocortical synaptoneurosomes. The primary effect of the steroids was to enhance the affinity of GABA for its receptors without much effect on the maximal uptake rate; the ED50 for GABA decreased from 66.4 +/- 5.7 to 8.9 +/- 1.2 microM in the presence of 20 microM 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one. Stimulation of 36Cl- uptake by high concentrations of the anesthetic steroid in the absence of exogenous GABA was not due to direct stimulation of GABAA receptors, as currently proposed, but is due to enhanced action of endogenous GABA, inasmuch as the steroid markedly increases GABA affinity for the receptors. Typically, endogenous GABA was maintained at near 1 microM by a Na(+)-dependent GABA transport system in the synaptoneurosomes. Elevation of its level with nipecotic acid, a specific inhibitor of the GABA transport system, or reduction with GABase, a GABA-scavenging system, increased or decreased, respectively, the steroid-induced bicuculline-sensitive 36Cl- uptake. At low concentrations of GABA (less than 2 microM), the stimulatory effect of 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one was markedly potentiated by pentobarbital but antagonized by 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one, a partial agonist of higher affinity. These observations, along with the structure-activity relationships of steroid analogs, strongly suggest the existence of a specific binding site for the steroids in GABAA receptors and led us to propose a minimal model in which two key common functional groups of anesthetic steroids, 3 alpha-OH- and 17 beta-polar substituents, interact with GABAA receptors (probably through hydrogen bondings) while their hydrophobic backbone remains in contact with the fatty acyl chains of membrane phospholipids.
Mol Pharmacol 1990 Mar
PMID:Studies on the mechanism of interactions between anesthetic steroids and gamma-aminobutyric acidA receptors. 215 55

The action of TBPS (tert-butylbicyclophosphorothionate) on spontaneous chloride channels recorded from porcine pars intermediate lobe cells in primary culture has been studied. This compound, which binds specifically to the gamma-aminobutyric acidA (GABAA) receptor complex, is known as a channel-gating (non-competitive) GABA antagonist. The present results show that TBPS reduces spontaneous chloride channel activity in a dose-dependent manner, with an IC50 equal to 55 nM, which is a value comparable to its affinity for the GABAA binding sites. Single-channel analysis revealed that TBPS affects neither the amplitude nor the open time of these spontaneous channels but prolongs the longer closed times, resulting in a dramatic decrease in opening probability.
Mol Pharmacol 1990 Apr
PMID:Electrophysiological study of tert-butylbicyclophosphorothionate-induced block of spontaneous chloride channels. 215 64

In situ hybridization histochemistry and RNA blots were used to study expression of glutamic acid decarboxylase (GAD) mRNA in rat caudate-nucleus and substantia nigra. In situ hybridization combined with computerized image analysis revealed that in the intact substantia nigra reticulata the cross-section area of GAD mRNA positive neurons were 25% larger in the dorsolateral part as compared with the ventromedial part. A unilateral ibotenic acid injection in caudate-putamen lesioned neurons, some of which project to the ipsilateral substantia nigra. An increased level of GAD mRNA was observed in substantia nigra ipsilateral to the lesion. Computerized image analysis of sections from in situ hybridization revealed an increase in the number of silver grains over GAD mRNA positive neurons in the dorsolateral substantia nigra reticulata ipsilateral to the lesion. However, no change was observed in the ventromedial part suggesting that GAD mRNA expression in this part of the nigra is less sensitive to inhibition by caudate-putamen afferents. In agreement with in situ experiments, RNA blots showed a 2-fold increased level of GAD mRNA in substantia nigra ipsilateral to the lesion. The increased GAD mRNA expression in the deafferented substantia nigra suggests a disinhibition of nigral GABA neurons, resulting in an increased utilization of GABA in these substantia nigra neurons.
Brain Res Mol Brain Res 1990 Apr
PMID:Increased expression of glutamic acid decarboxylase mRNA in rat substantia nigra after an ibotenic acid lesion in the caudate-putamen. 215 80

The localization of gamma-aminobutyric acid-A (GABAA) receptors (GABAA-R) in the lower brainstem of the rat was examined by means of in situ hybridization histochemistry using an oligonucleotide probe to the sequence of the alpha 1 subunit (GABAA-R alpha 1). Strongly labeled neurons were found in the cranial motor nuclei, the dorsal motor nucleus of the vagus, reticular formation (large neurons), lateral vestibular nucleus, dorsal nucleus of the lateral lemniscus, central nucleus of the inferior colliculus, intermediate and white layers of the superior colliculus, red nucleus and substantia nigra. In addition, moderately labeled cells were abundant in the nucleus of the solitary tract, medial and inferior vestibular nuclei, parabrachial area, dorsal and ventral tegmental nuclei of Gudden, central gray matter, ventral nucleus of the lateral lemniscus, and reticular formation (small neurons). This study has therefore revealed some of the target neurons of GABA-containing fibers in the lower brainstem.
Brain Res Mol Brain Res 1990 May
PMID:Localization of GABAA-receptor alpha 1 subunit mRNA-containing neurons in the lower brainstem of the rat. 216 8

The pharmacological properties and modulation by lithium of the kainate (KA) receptor system coupled to the evoked release of [3H]-gamma-aminobutyric acid [( 3H]GABA) from purified populations of striatal neurons in primary culture were examined. KA evoked a dose-dependent (EC50, 100 microM) and saturable increase in [3H]GABA release from striatal neurons that was unaffected by the removal of extracellular calcium and resistant to the actions of tetrodotoxin. The release of [3H]GABA evoked by 100 microM KA was attenuated in a dose-dependent manner by the following excitatory amino acid antagonists (IC50):6-cyano-2, 3-dihydroxy-7-nitroquinoxaline (2 microM),2,3-dihydroxy-6,7-dinitroquinoxaline (2 microM), kynurenate (0.3 mM), and gamma-D-glutamylglycine (2 mM). The antagonist properties of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline, kynurenate, and gamma-D-glutamylglycine were competitive in nature, inducing parallel rightward shifts of the KA dose-response curves. At concentrations at which it did not significantly increase basal levels of [3H]GABA release, quisqualate attenuated in a dose-dependent manner (IC50, 10 microM) the release due to 100 microM KA. The quisqualate receptor agonist alpha-amino-3-hydroxyisoxazolepropionic acid (AMPA), however, exerted a biphasic effect on 100 microM KA-evoked release of [3H]GABA. At lower concentrations of AMPA (0.1-10 microM), the release due to 100 microM KA was potentiated 25-50%; at higher concentrations (greater than 10 microM) AMPA induced a dose-dependent (IC50, 100 microM) attenuation of KA-evoked release. The release of [3H]GABA due to 100 microM KA was significantly potentiated by the replacement of sodium with lithium in the extracellular medium. A significant potentiation (20-30%) was detected with as little as 5-10 mM lithium, and maximal effects (100-110% increase) were obtained with 50-75 mM lithium. Replacement of sodium with choline or N-methyl-D-glucamine could not mimic the actions of lithium. Lithium (25 mM) also induced a 4-fold increase in the levels of endogenous GABA release due to 100 microM KA. Whole-cell voltage-clamp recordings of these striatal neurons indicated that the 100 microM KA-induced inward current was not significantly altered in the presence of 25 mM lithium. Lithium attenuated vasoactive intestinal polypeptide-stimulated cyclic AMP formation by 50%, with a dose dependence similar to that of its actions on KA-evoked release. The results of this study demonstrate a distinct pharmacological profile for the KA receptor system coupled to the evoked release of [3H]GABA from striatal neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1990 Aug
PMID:Kainate receptors coupled to the evoked release of [3H]-gamma-aminobutyric acid from striatal neurons in primary culture: potentiation by lithium ions. 216 3

GABA (gamma-aminobutyric acid), the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by opening a chloride channel integral to the GABAA receptor. This action is potentiated by both benzodiazepine and barbiturate drugs. Since the isolation of cDNAs encoding GABAA receptor alpha 1 and beta 1 subunits, a further eight subunits have been identified. These subunits show GABAA receptor heterogeneity, unpredicted from classical pharmacological studies. I now report the isolation of a mouse cDNA clone encoding a novel GABAA receptor alpha subunit. The striking feature of this subunit is its regional distribution in the mouse brain. Northern hybridization and in situ hybridization experiments demonstrate that the subunit mRNA is expressed only in cerebellar granule cells. This is the first demonstration of the exclusive presence of a neuroreceptor subtype in a single neuronal cell type.
J Mol Biol 1990 Aug 05
PMID:Novel GABAA receptor alpha subunit is expressed only in cerebellar granule cells. 216 78

In order to assess changes in enkephalin release and biosynthesis, the levels of the tripeptide Tyr-Gly-Gly (YGG), a characteristic extracellular metabolite of enkephalins, and of the proenkephalin mRNA in mouse striatum were evaluated after a single administration of GABAergic agents. Significant and long-lasting decreases in steady state YGG levels were elicited by muscimol, a gamma-aminobutyric acid-A (GABAA) receptor agonist, diazepam, a benzodiazepine receptor agonist, or aminooxyacetic acid, a GABA-transaminase inhibitor. In addition, muscimol offset the elevation of striatal YGG elicited by bestatin, an aminopeptidase inhibitor, which entirely drives the released enkephalins into the metabolic pathway operated by enkephalinase (EC 3.4.24.11). Diazepam potentiated the effect of muscimol so that the YGG decrease induced by the combination of these two drugs was maximal after 30 min (-60%) and still significant (-40%) after 6 h, this potentiation being antagonized by pre-treatment with Ro 15-1788, a specific benzodiazepine receptor antagonist. By contrast [Met5]enkephalin steady-state levels were marginally affected by GABAergic agents, being only slightly reduced 6 h after the combination of muscimol and diazepam. After 3 h the same treatment also reduced by about 30% the level of proenkephalin mRNA, this change being maximal after 6 h (-45%) and still present after 24 h. These compared changes in various indexes of enkephalin neuron activity suggest that stimulation of GABAA receptors depresses enkephalin release immediately and for several hours, whereas preproenkephalin gene expression is decreased in a somewhat delayed and longer lasting manner. These patterns of temporal changes in biosynthesis and release of the neuropeptide presumably account for the limited changes in its steady state levels.
Brain Res Mol Brain Res 1990 Aug
PMID:Enkephalin biosynthesis and release in mouse striatum are inhibited by GABA receptor stimulation: compared changes in preproenkephalin mRNA and Tyr-Gly-Gly levels. 217 Aug


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