Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the belief that homocysteine-induced convulsions might be related to alterations in brain gamma-aminobutyric acid metabolism, we have studied the action of this amino acid on the activity of glutamic decarboxylase (GAD, EC 4.1.1.15) and gamma-aminobutyrate aminotransferase (EC 2.6.1.19) of mouse brain in vitro DL-homocysteine competitively inhibited GAD with respect to both L-glutamate and pyridoxal 5'-phosphate. The respective Ki's were 3.8 mM and 0.3 mM. The activity of GABA-T also was altered in the presence of DL-homocysteine. A competitive inhibition (Ki = 6 mM) was observed with gamma-aminobutyric acid, and an uncompetitive inhibition with respect to pyridoxal 5'-phosphate and alpha-ketoglutarate. These results are explained in terms of a dual action of homocysteine on each of the enzymes: one involving a competition for substrate binding site and the other involving the formation of an inactive inhibitor-cofactor complex. The significance of the inhibition of these enzymes of gamma-aminobutyric acid metabolism is discussed in relation to the convulsant action of homocysteine.
Can J Biochem 1977 Sep
PMID:The mode of action of homocysteine on mouse brain glutamic decarboxylase and gamma-aminobutyrate aminotransferase. 90 1

To implicate gamma-aminobutyric acid (GABA) as an afferent neurotransmitter (AN), the localization of GABA synthesizing and degradation enzymes; L-glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) was investigated by light and electron microscopy immunocytochemistry in guinea pig vestibular cristae and ganglion cells (GC). GAD-like immunoreactivity was exclusively confined to the sensory hair cell (HC) cytoplasm, suggesting that GAD synthesizes GABA in the HC. GABA-T like immunoreactivity was found within HC, nerve calyces, nerve fibers, and GC, suggesting its participation in terminating transmitter action. These results demonstrate the existence of a GABAergic system in the guinea pig vestibule and strongly support GABA as a vestibular AN.
Brain Res 1992 Sep 04
PMID:Immunocytochemical evidence for an afferent GABAergic neurotransmission in the guinea pig vestibular system. 132 17

Vigabatrin is a specific gamma-aminobutyric acid transaminase inhibitor. The clinical use of this drug in the treatment of epilepsy has been sporadically linked to the development of psychosis. Using 123I-IBZM, a specific dopamine D2 receptor ligand and single photon emission tomography (SPET), one month of treatment with vigabatrin was associated with a decrease in specific binding of 123I-IBZM to D2 receptors in the left hemisphere basal ganglia. This change may provide one explanation for the development of psychosis in vulnerable patients.
J Neurol Neurosurg Psychiatry 1992 Sep
PMID:Effect of vigabatrin on striatal dopamine receptors: evidence in humans for interactions of GABA and dopamine systems. 132 38

D1 dopamine receptors are present on terminals of striatal neurons to the pars reticulata of the substantia nigra in the rat. Here we have studied the effect of the activation of these receptors on the synthesis of gamma-aminobutyric acid (GABA) in slices of the pars reticulata of the substantia nigra isolated from 6-hydroxydopamine-lesioned rats. The synthesis was judged by the accumulation of GABA after inhibiting GABA transaminase with aminooxyacetic acid. Both dopamine and SCH 23390, a D1 agonist, stimulated the synthesis. The effect of both compounds was blocked by SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. In the absence of receptor activation, the synthesis was very slow. The results suggest a trophic influence of dopamine upon the synthesis of GABA via D1 receptors.
Neurosci Lett 1992 Sep 28
PMID:Activation of D1 receptors stimulates accumulation of gamma-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats. 146 65

Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy. The excitotoxic hypothesis of epileptic cell death [Olney, J. W. (1978) in Kainic Acid as a Tool in Neurobiology, eds. McGeer, E., Olney, J. W. & McGeer, P. (Raven, New York), pp. 95-121; Olney, J. W. (1983) in Excitotoxins, eds. Fuxe, K., Roberts, P. J. & Schwartch, R. (Wenner-Gren International Symposium Series, Macmillan, London), Vol. 39, pp. 82-96; and Rothman, S. M. & Olney, J. W. (1986) Ann. Neurol. 19, 105-111] predicts an imbalance between excitation and inhibition, which occurs probably as a result of hyperactivity in afferent pathways or impaired inhibition. In the present study, we investigated whether the enhancement of gamma-aminobutyric acid (GABA)-mediated (GABAergic) inhibition of neurotransmission by blocking the GABA-metabolizing enzyme, GABA transaminase, could influence the histopathological and/or the behavioral outcome in this epilepsy model. We demonstrate that the loss of pyramidal cells and hilar somatostatin-containing neurons can be abolished by enhancing the level of synaptically released GABA, and that the preservation of hippocampal structure is accompanied by a significant sparing of spatial memory as compared with placebo-treated controls. These results suggest that enhanced GABAergic inhibition can effectively block the pathophysiological processes that lead to excitotoxic cell death and, as a result, protect the brain from seizure-induced cognitive impairment.
Proc Natl Acad Sci U S A 1991 Sep 01
PMID:Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. 165 57

Effects of drugs which enhance or reduce GABAergic neurotransmission upon conflict behavior were evaluated with a modified Vogel procedure which was shown to be insensitive to variations in motivation to drink and to the analgesic effects of morphine. In addition, the effects of these drugs on ambulatory activity and motor execution were quantified. For comparison, the benzodiazepines diazepam and chlordiazepoxide were used. Anticonflict actions of diazepam were obtained with a shock current of 0.25 mA but not with 0.05 or 0.5 mA, whereas the proconflict effect of FG7142 was obtained with 0.05 mA but not with higher currents. Diazepam and chlordiazepoxide had anxiolytic effect in a dose similar to that required to reduce ambulatory activity, but below that needed to affect motor execution. At doses high enough to impair motor execution, anticonflict effects were considerable. The GABA-A receptor agonist THIP and the GABA-B receptor agonist baclofen lacked effect on conflict behavior in moderate doses, which reduced ambulatory activity. In doses which produced motor deficiencies these drugs reduced licking both in the conflict test and when tested without shock administration. The effects of the GABA transaminase inhibitors gamma-acetylene GABA and sodium valproate were similar to those of the receptor agonists. The GABA reuptake inhibitor SKF 100330A produced anticonflict effect in a dose below that needed to reduce ambulatory activity, but lacked effect on conflict behavior in higher doses. The GABA antagonist picrotoxin, and the GABA synthesis inhibitors 4-deoxypyridoxine and isoniazide, reduced licking both in the absence and presence of shock, and affected motor functions in the same doses. Bicuculline, at the doses used, had no behavioral effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Naunyn Schmiedebergs Arch Pharmacol 1991 Sep
PMID:GABAergic drugs and conflict behavior in the rat: lack of similarities with the actions of benzodiazepines. 166 Jan 3

Previous studies found that injection of the GABA uptake inhibitor nipecotic acid into the nucleus tractus solitarius (NTS) increases arterial pressure. This effect of nipecotic acid was not antagonized by the selective GABAA receptor blocking agent bicuculline, suggesting that the action of nipecotic acid was mediated through an action of GABA on GABAB receptors in the NTS. The present studies examined this issue using a newly described GABAB antagonist, phaclofen. Injection of phaclofen (4 nmol in 100 nl artificial CSF) into the NTS of chloralose-anesthetized rats produced a slight decrease in arterial pressure (-8 +/- 2 mmHg) lasting less than 1 min. Smaller doses had no effect. Phaclofen antagonized in a dose-dependent (0.5-4 nmol) manner the increase in arterial pressure produced by injection into the NTS of the GABAB agonist baclofen (5-100 pmol). In contrast, phaclofen had no effect on the pressor response elicited by injection into the NTS of the GABAA agonist muscimol. Phaclofen (4 nmol) injected into the NTS totally reversed the increase in blood pressure elicited by injection into the NTS of a maximally effective dose of nipecotic acid (10 nmol). Phaclofen also inhibited the pressor response elicited by injection into the NTS of another indirectly acting GABA agonist, gamma-vinylGABA (GVG). Although GVG is an effective inhibitor of GABA transaminase, the enzyme involved in the metabolism of GABA, the time course of inhibition of GABA transaminase evoked by GVG was not consistent with the pressor response being produced by this mechanism. However, the pressor response elicited by GVG is consistent with its reported ability to inhibit GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res 1990 Sep 03
PMID:Endogenous GABA acts on GABAB receptors in nucleus tractus solitarius to increase blood pressure. 217 40

Agents modifying GABAergic neurotransmission were administered to ovariectomized rats treated with different doses of estradiol benzoate (EB) + progesterone (P) or with EB alone. Hormone treatments were designed to induce an intermediate level of receptivity in order to be able to observe both stimulatory and inhibitory effects on lordosis behavior. Both the GABAA receptor agonist THIP and the GABAB receptor agonist baclofen inhibited lordosis behavior at doses from 20 and 5 mg/kg, respectively. The GABA transaminase inhibitor gamma-acetylen GABA (GAG) and the GABA agonist 3-aminopropanesulfonic acid had no effects, even when high doses were administered. The GABAA receptor antagonist bicuculline had no effect by itself nor did it block the effects of THIP. It is therefore suggested that the GABAA receptor is of slight importance in the control of lordosis behavior. No evidence could be found supporting the hypothesis that an interaction between P and GABA is important for hormone-induced receptivity. It does not appear likely that motor disturbances are responsible for the inhibitory effects of baclofen and THIP. The exact mechanism by which these drugs inhibit lordosis behavior is not clear at present.
Horm Behav 1989 Sep
PMID:GABAergic drugs and lordosis behavior in the female rat. 255 11

The GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate were administered intraperitoneally and their effects on locomotor activity, motor execution and sexual behavior were analyzed. It was found that sodium valproate, administered 15 min before observation, reduced locomotor activity only at a dose of 200 mg/kg. Doses of 100 and 400 mg/kg had no effect. Motor execution was impaired in a dose-dependent way, the lowest effective dose being 200 mg/kg. Sexual behavior was also dose-dependently reduced. Sodium valproate, administered 60 min before observation, inhibited all behaviors. The lowest effective dose was 200 mg/kg for locomotor activity and 400 mg/kg for motor execution and sexual behavior. GAG also inhibited all behavior, in doses ranging from 25 mg/kg (locomotor activity) to 100 mg/kg (motor execution and sexual behavior). The data showed that there is no relation between effects on locomotor activity and the effects on sexual behavior, whereas sexual behavior is inhibited whenever motor execution is impaired. Moreover, there is no correlation between effects on locomotor activity and motor execution. It is suggested that GABA transaminase inhibitors effect sexual behavior only indirectly, via an impairment of motor execution. Therefore it is doubtful whether GABAergic mechanisms play any role in the normal regulation of sexual behavior.
Pharmacol Biochem Behav 1987 Sep
PMID:Differential effects of GABA transaminase inhibitors on sexual behavior, locomotor activity, and motor execution in the male rat. 311 62

beta-Endorphin, Met-enkephalin, substance P, and somatostatin concentrations were evaluated in the hypothalami of rats treated either acutely or chronically (15 days) with sodium valproate, diphenylhydantoin, phenobarbital, or ethosuximide. All of these drugs, with the exception of ethosuximide, induced significant decreases in beta-endorphin concentrations after acute treatment, while only sodium valproate induced a decrease after chronic treatment. The acute and chronic effects of sodium valproate were also produced by aminooxyacetic acid, an inhibitor of gamma-aminobutyric acid (GABA) transaminase, while another GABA transaminase inhibitor, ethanolamine-O-sulphate, and THIP, a GABA receptor agonist, were effective after acute administration. Metenkephalin, substance P, and somatostatin concentrations were never affected by the drugs used. The present results, indicating that antiepileptic agents specifically decrease beta-endorphin concentrations, seem to correlate well with the capacity of these agents to blunt the epileptic activity of the peptides tested. Moreover, our data suggest that GABA may be involved in the anticonvulsant-induced reduction of beta-endorphin concentrations.
J Neurochem 1984 Sep
PMID:Antiepileptic agents affect hypothalamic beta-endorphin concentrations. 620 24


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