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)

The involvement of gamma-aminobutyric acid (GABA) in regulation of pituitary gonadotropin-II (GTH-II) release was studied in the goldfish. Intraperitoneal injection of GABA (300 micrograms/g) stimulated an increase in serum GTH-II levels at 30 min postinjection. The GABAA receptor agonist muscimol (0.1-10 micrograms/g) stimulated GTH-II in a dose-dependent manner. Baclofen, a GABAB receptor agonist, had a small but significant stimulatory effect at 1 and 10 micrograms/g; the amount of GTH-II released in response to baclofen was significantly less (P < 0.05) than that released by muscimol. Pretreatment of goldfish with bicuculline, a GABAA receptor antagonist, but not saclofen, a GABAB receptor antagonist, blocked the stimulatory effect of GABA on serum GTH-II. Elevation of brain and pituitary GABA levels with the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG), decreased hypothalamic and pituitary dopamine (DA) turnover rates, indicating that GABA may stimulate GTH-II release in the goldfish by decreasing dopaminergic inhibition of GTH-II release. The release of GTH-II stimulated by muscimol and GVG was potentiated by pharmacological agents that decrease inhibitory dopaminergic tone, indicating that DA may also inhibit GABA-stimulated GTH-II release. Based on the linear 24-h accumulation of GABA in brain and pituitary after GVG injection, implantation of testosterone, estradiol, or progesterone, previously shown to regulate the serum GTH-II release response to gonadotropin-releasing hormone and GABA, was also found to modulate GABA synthesis in the brain and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABA stimulation of gonadotropin-II release in goldfish: involvement of GABAA receptors, dopamine, and sex steroids. 839 53

Vigabatrin (gamma-vinyl-GABA), a structural analogue of GABA, is a selective inhibitor of GABA transaminase. Vigabatrin has been effective in patients with refractory epilepsy. We treated patients with complex partial seizures and some of them also with secondary generalized seizures. Vigabatrin was administered as "add on therapy" (Table 1) and monotherapy (Table 2). As to table 1, concerning a variety of treatments and too few patients we could not reach any definitive statistical conclusion (paired Student's t test not significant). In table 2 the paired Student's t test was significant with p < 0.01. Longer follow-up is needed to determine whether the clinical effect is maintained and no severe side effects appear.
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PMID:[Gamma-vinyl-GABA: the first trials in Italy]. 847 29

The pharmacologic treatment of many neuropsychiatric disorders (Alzheimer's disease, schizophrenia, depressive illness) has been targeted at the central hypothesis that defects in a single neurotransmitter system underlie the pathophysiology of the disease state. With the recognition that such treatments have not been efficacious consistently, recent drug development has been directed at altering other functionally linked neurotransmitters involved in these diseases. Using positron emission tomography, we have noninvasively investigated the effects of two noncholinergic drugs on the release of acetylcholine. By examining the effects of gamma-vinyl gamma-aminobutyric acid (GABA) (a GABA transaminase inhibitor) or altanserin (a serotonergic antagonist) on the regional binding of 11C-benztropine in the primate brain (Papio anubis), we demonstrated that drugs acting upon either GABAergic or serotonergic neurons produce profound regional changes in acetylcholine release. These findings indicate that the mechanisms of action and the subsequent therapeutic efficacy of these centrally acting drugs may be linked to their multitransmitter effects. This application of positron emission tomography represents an extremely promising experimental approach that can be directed towards elucidating abnormalities in neurotransmitter modulation relevant to disease progression and pharmacologic treatment.
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PMID:Modulation of central cholinergic activity by GABA and serotonin: PET studies with 11C-benztropine in primates. 851 23

This study has examined whether changes in endogenous GABA concentrations influence GABAA receptor subunit mRNA expression in vivo. Increased GABA concentrations were achieved by treating female rats with gamma-vinyl-GABA (15 mg/100 g), an irreversible inhibitor of the GABA transaminase, daily for three days. High performance liquid chromatography analysis of brain punches from specific brain regions showed that gamma-vinyl-GABA treatment resulted in approximately two-fold increases in brain GABA content. Using in situ hybridization techniques with specific 35S-labelled oligonucleotides, the mRNA expression of the alpha 1, alpha 2, beta 2, beta 3, gamma 1 and/or gamma 2 subunits of the GABAA receptor was quantified in various brain regions including the medial preoptic nucleus, bed nucleus of the stria terminalis, bed nucleus of the anterior commissure, supraoptic and paraventricular nuclei of the hypothalamus, globus pallidus and cingulate cortex. Silver grain density analysis showed that gamma-vinyl-GABA treatment induced a significant 35 and 49% decrease in gamma 1 mRNA expression in the medial preoptic nucleus and the principle encapsulated nucleus of the bed nucleus of the stria terminalis respectively, and a significant 20% decrease in alpha 2 mRNA expression in the cingulate cortex. Expression of alpha 2 and beta 3 in the former areas was unchanged as was alpha 1, beta 2, beta 3 and gamma 2 subunit expression in the cingulate cortex. Elevation of brain GABA levels also resulted in a specific and significant 17% increase in gamma 2 mRNA expression in the supraoptic nucleus. In the globus pallidus, gamma-vinyl-GABA treatment induced a significant 29% increase in alpha 1 mRNA expression combined with 19 and 30% decreases in beta 2 and gamma 2 mRNA expression, respectively. Levels of GABAA receptor subunits expressed in the bed nucleus of the anterior commissure (alpha 2, beta 3, gamma 1) and paraventricular nucleus (alpha 1, alpha 2, beta 2, gamma 2) were not changed by gamma-vinyl-GABA treatment. These results provide in vivo evidence for a region- and subunit-specific regulation of GABAA receptor subunit mRNA levels following the elevation of brain GABA concentrations and suggest that endogenous GABA levels influence GABAA receptor subunit mRNA expression.
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PMID:In vivo regulation of specific GABAA receptor subunit messenger RNAs by increased GABA concentrations in rat brain. 886 39

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is not solely located in the CNS, it and the enzymes responsible for its synthesis (glutamic acid decarboxylase, GAD, EC 4.1.1.15) and catabolism (GABA-transaminase, GABA-T, EC 2.6.1.19) are also present in non-neuronal organs. Following 2, 8 and 21 day oral administration of ethanolamine-O-sulphate (EOS) and gamma-vinyl GABA (GVG), two irreversible inhibitors of GABA-T, the GABA content and activities of GAD and GABA-T in rat brain, liver and kidney, and the GABA content of plasma were determined: GABA-T activity was significantly decreased (over 80%) in liver, brain and kidney, although there was 2-3 times the residual activity left in the brain compared with the peripheral organs. GABA content was subsequently significantly elevated in the liver (300-1500%), plasma (200-300%) and brain (200-300%), although, surprisingly, the kidney GABA content was reduced (by 60-70%) compared with control. GAD activity was decreased following 8 day treatment in liver and brain. Kidney GAD was reduced at all time points. These two compounds are anticonvulsant, GVG is used clinically for the treatment of epilepsy but it seems that these drugs have significant peripheral effects.
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PMID:Effects of chronic oral treatment with GABA-transaminase inhibitors on the GABA system in brain, liver, kidney, and plasma of the rat. 893 45

1. The effects of 2, 8 and 21 day oral treatment with the specific gamma-aminobutyric acid transaminase (GABA-T) inhibitors gamma-vinyl GABA (GVG) and ethanolamine O-sulphate (EOS) on brain GABA levels, GABA-T activity, and basal and stimulated GABA release from rat cross-chopped brain hippocampal slices was investigated. 2. Treatment with GABA-T inhibitors lead to a reduction in brain GABA-T activity by 65-80% compared with control values, with a concomitant increase in brain GABA content of 40-100%. 3. Basal hippocampal GABA release was increased to 250-450% of control levels following inhibition of GABA-T activity. No Ca2+ dependence was observed in either control or treated tissues. 4. GVG and EOS administration led to a significant elevation in the potassium stimulated release of GABA from cross-chopped hippocampal slices compared with that of controls. Although stimulated GABA release from control tissues was decreased in the presence of a low Ca2+ medium, GVG and EOS treatment abolished this Ca2+ dependency. 5. GABA compartmentalization, Na+ and Cl- coupled GABA uptake carriers and glial release may provide explanations for the loss of the Ca2+ dependency of stimulated GABA release observed following GVG and EOS treatment. 6. Administration of GABA-T inhibitors led to increases in both basal and stimulated hippocampal GABA release. However, it is not clear which is the most important factor in the anticonvulsant activity of these drugs, the increased GABA content 'leaking' out of neurones and glia leading to widespread inhibition, or the increase in stimulated GABA release which may occur following depolarization caused by an epileptic discharge.
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PMID:Effect of chronic treatment with the GABA transaminase inhibitors gamma-vinyl GABA and ethanolamine O-sulphate on the in vitro GABA release from rat hippocampus. 935 12

Gamma-vinyl GABA (GVG, also referred to as vigabatrin), an irreversible inhibitor of GABA transaminase (GABA-T), raises levels of GABA in nerve terminals, inhibits striatal dopamine release, and attenuates cocaine-induced increases in extracellular dopamine in the striatum and nucleus accumbens. In order to determine the action of GVG on dopamine-mediated reward, we examined its effects on the threshold for rewarding brain stimulation in male F-344 rats. GVG dose-dependently raised brain stimulation reward (BSR) thresholds at doses of 200, 300, and 400 mg/kg without significant effects on motor performance as measured by response latencies. In order to determine if GVG had similar modulatory effects on cocaine-induced lowering of BSR thresholds, the effective doses of GVG were co-administered with 2.5 and 5.0 mg/kg cocaine, doses that significantly lower BSR thresholds. The 400 mg/kg dose of GVG significantly blocked the lowering of thresholds seen at each dose of cocaine. Cocaine in combination with 200 or 300 mg/kg GVG, doses of GVG that significantly raise BSR thresholds, resulted in thresholds not significantly different from those obtained with cocaine alone. These data demonstrate that, at the doses tested, GVG is more effective at modulating basal reward thresholds that at modulating thresholds lowered by cocaine, implying that as dopaminergic activity increases, GABAergic activity must also increase in order to exert its inhibitory influence on dopaminergic activity.
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PMID:Gamma-vinyl GABA attenuates cocaine-induced lowering of brain stimulation reward thresholds. 937 39

Vigabatrin (gamma-vinyl GABA) is an antiepileptic drug and blocks GABA transaminase activity resulting in elevations in cellular GABA levels in the brain. Nipecotic acid (NPA) promotes release of GABA from neonatal optic nerve astrocytes, resulting in a bicuculline-sensitive depolarization of the optic nerve axons. The NPA-induced depolarization of vigabatrin-treated rats (100 mg/kg, i.p.) more than doubled, suggesting an elevation in free GABA levels; the GABA transporter inhibitor, NO-711 reduced the depolarization. These results are consistent with the known ability of vigabatrin to block the GABA degradation enzyme GABA-transaminase, suggesting that vigabatrin elevates astrocytic GABA levels, thereby favoring greater release of GABA through the GABA transporter.
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PMID:Vigabatrin enhances promoted release of GABA in neonatal rat optic nerve. 955 81

Helium pressure of > 20 bar causes neuroexcitatory changes referred to as the high pressure neurological syndrome. In rodents, symptoms include locomotor and motor activity (LMA), myoclonia and, at greater pressure, convulsions. We studied the effects of the GABA reuptake inhibitor nipecotic acid, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), the GABAA receptor agonist muscimol, and the GABAB receptor agonist baclofen. Whatever the drug used, bilateral administration in the substantia nigra reticulata (SNR) or in the substantia nigra compacta (SNC) showed no significant effects on myoclonia. In contrast, administration in the SNR of nipecotic acid, GVG, and baclofen resulted in a significant decrease of LMA; administration of muscimol in the SNR increased LMA. No significant effect was seen when drugs were injected in the SNC. These results suggest that changes in GABA transmission in the SNR, but not in the SNC, play a crucial role in the control of motor activity and the regulation of movement.
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PMID:Modulation by GABA transmission in the substantia nigra compacta and reticulata of locomotor activity in rats exposed to high pressure. 963 26

Effects of gamma-vinyl-GABA (GVG), an antiepileptic drug that inhibits GABA transaminase and increases extracellular GABA concentrations in the brain, were investigated on the morphine abstinence syndrome (AS) in male Wistar rats. Two morphine pellets (75 mg morphine base in each) were implanted subcutaneously on the back of the rats. Seventy-two hours after the morphine implantation, naloxone (NL, 2 mg kg-1) was injected intraperitoneally (i.p.) to induce precipitated morphine AS. GVG was administered at the doses of 250 mg kg-1 (n = 11) and 500 mg kg-1 (n = 11) i.p. 24 h prior to AS and at the dose of 500 mg kg-1 (n = 13) i.p. 6 h prior to AS. Immediately after NL injections, rats were observed for 5 min and AS signs (jumping, teeth chattering, wet dog shake, diarrhoea, ptosis and defecation) were assessed. The behavioural signs of GVG-treated rats were compared with the control groups (n = 10) during the AS. Jumping, wet dog shake, teeth chattering were found to be significantly increased in all of the GVG-treated groups. Ptosis was found to have increased in only 500 mg kg-1 GVG groups. GVG potentiated the severity of morphine AS signs. GVG does not seem to have any therapeutic potential for treatment of morphine abstinence unlike some other drugs that enhance GABAergic transmission.
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PMID:Gamma-vinyl-GABA potentiates the severity of naloxone-precipitated abstinence signs in morphine-dependent rats. 969 54


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