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 effects of aminooxyacetic acid (AOAA), an aspartate aminotransferase (AAT) inhibitor, L-canaline, an ornithine aminotransferase inhibitor, and gamma-acetylenic GABA and gabaculine, both gamma-aminobutyric acid transaminase (GABA-T) inhibitors, on the release of aspartate from slices of rat medulla oblongata and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2(+)-dependent stimulus-evoked release of endogenous aspartate. AOAA (10(-4) and 10(-3) M) decreased the evoked release of aspartate in the medulla oblongata but not in the hippocampus. In addition, AOAA produced a decrease in the spontaneous efflux and tissue content of aspartate in the medulla oblongata. L-Canaline (5 x 10(-5) M), gamma-acetylenic GABA (10(-4) M) and gabaculine (10(-5) M) did not affect the evoked release of aspartate in the medulla oblongata, while these agents produced a decrease in spontaneous efflux and tissue content of aspartate. These findings suggest that AAT participates in the synthesis of transmitter aspartate in the medulla oblongata of the rat. It appears that there are the pools of transmitter aspartate and non-transmitter aspartate in the rat medulla oblongata.
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PMID:Electrical stimulation-evoked release of endogenous aspartate from rat medulla oblongata slices. Effects of inhibitors of aspartate aminotransferase and GABA transaminase. 234 2

The effects of systemically injected caerulein, a cholecystokinin octapeptide analogue, on GABA content and turnover have been studied in various regions of rat brain. Caerulein decreased GABA levels in the nucleus accumbens, tuberculum olfactorium and substantia nigra and diminished GABA turnover rates in the striatum, nucleus accumbens and substantia nigra, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA). These results indicate the effect of caerulein on the utilization of GABA in specific cerebral regions and suggest that the GABAergic system is involved in the mechanism of action of peripherally administered caerulein.
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PMID:Changes in GABA content and turnover in discrete regions of rat brain after systemic administration of caerulein. 234 75

Vigabatrin (gamma-vinyl-GABA), an irreversible inhibitor of gamma-aminobutyric acid transaminase, has been reported to be effective in the treatment of refractory epilepsies. Animal toxicology studies have shown that long-term application of vigabatrin induces intramyelinic edema and microvacuolation of the white matter in non-primate species. However, clinical and neuropathological studies of patients exposed to long-term vigabatrin treatment have, so far, provided no evidence for microvacuolation in the human brain. We report on the histopathological findings of selective amygdalohippocampectomy specimens from a 36-year-old female patient treated with vigabatrin for a period of 11.5 months, and from 2 control patients with chronic refractory temporal lobe seizures. All specimens showed changes associated with chronic epileptic seizures including focal neuronal loss and hippocampal gliosis. Microvacuoles, intramyelinic edema or other manifestations of neurotoxic damage were not observed in vigabatrin exposed tissue, supporting the view that this compound may not exert hippocampal neurotoxicity in humans.
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PMID:Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of microvacuoles. 238 87

1. Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase. 2. To further evaluate the effects and mechanism of action of GVG in the human brain, we measured acetylcholinesterase (AChE) activity and levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), cyclic nucleotides (cAMP, cGMP), total GABA (TGABA), and GVG in CSF of 78 patients with complex partial epilepsy. The CSF samples were taken at baseline and after 3 months of GVG administration (3 g GVG per day). Thereafter, the responders (= 50% decrease in number of seizures) were divided (double-blind) into two groups that received either 1.5 g or 3 g of GVG per day for the next 3 months. The third CSF sample was taken after this double-blind period. 3. TGABA levels were increased during the GVG treatment (p less than 0.001). In the whole group of patients AChE, HVA, 5-HIAA, and cAMP did not differ from baseline values, cGMP levels were slightly elevated after 3 months of GVG administration (p = 0.019), but were no longer elevated after 6 months. Responders had slightly lower AChE activity than nonresponders (p = 0.041). After 6 months of drug treatment the cGMP levels of patients receiving 1.5 g of GVG did not differ from those receiving 3 g. 4. In conclusion, GVG administration elevates levels of TGABA in the CSF without any clear of constant change to cholinergic and aminergic transmission or effect on cyclic nucleotides. Our study further emphasizes the specific mechanism of action of GVG via GABAergic transmission.
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PMID:Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study. 245 56

The main objective of this work was to study the role of the GABAergic system on the convulsions elicited by the organochlorine insecticide lindane. The concentration of lindane in rat brain at the onset of the first tonic convulsion was taken as the endpoint for the neurotoxic action of the insecticide administered by intravenous infusion. Pretreatment with the GABA agonists muscimol and progabide, the GABA uptake blocker SK&F 89976-A, the GABA transaminase inhibitor gamma-acetylenic GABA, and the GABA indirect agonist phenobarbital significantly increased the threshold concentration of lindane in brain required to induce convulsions. The GABA agonist THIP, the GABA competitive antagonist bicuculline, and the prodrug cetyl-GABA had no effect on the brain level of lindane required to induce seizures. The noncompetitive GABA antagonists, picrotoxinin and pentylenetetrazol, significantly decreased the brain concentration of lindane needed to elicit convulsions. The concentration of GABA in the brain of lindane-treated rats was only modified by the significant increase produced after gamma-acetylenic GABA pretreatment. These results show that the convulsions elicited by lindane can be facilitated by some GABA antagonists and antagonized by GABA mimetics, especially those that enhance GABA functionality. The present data are consistent with the proposed in vitro competition of lindane for the picrotoxinin binding site associated with the Cl- ionophore of the GABAA receptor, and suggest that lindane may also interact in vivo with this site.
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PMID:GABAergic modulation of lindane (gamma-hexachlorocyclohexane)-induced seizures. 247 71

Slices of rat temporo-parietal cortex were prelabeled with gamma-[3H]aminobutyric acid ([3H]GABA), in the presence of the glial GABA uptake inhibitor beta-alanine. The slices were then superfused with a medium containing the GABA transaminase inhibitor aminooxyacetic acid and stimulated electrically (5 min, 2 msec, 36 mA at 5 or 10 Hz), in the presence of the neuronal GABA reuptake inhibitor SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid] and of beta-alanine. Representative experiments showed that the tritium released could be accounted for almost entirely by authentic [3H]GABA. The electrically evoked overflow of [3H]GABA was tetrodotoxin sensitive and largely calcium-dependent. Exogenous GABA, added to the superfusion medium at 3 to 30 microM, reduced in a concentration-dependent manner the electrically evoked (5 Hz) release of [3H]GABA. The GABAB receptor agonist (-)-baclofen, but not the GABAA receptor agonist muscimol, mimicked GABA and produced a concentration-inhibition curve almost superimposable to that of the natural transmitter. The effects of GABA and of (-)-baclofen were much more pronounced at 5 than at 10 Hz. The GABA-induced inhibition of [3H]GABA release was sensitive to the novel GABAB receptor antagonist beta-(p-chlorophenyl)-3-amino propyl phosphonic acid which, by itself, increased the [3H]GABA overflow. The inhibitory effect of GABA was not counteracted by the GABAA receptor antagonists bicuculline or SR 95531 [2-(3'-carbethoxy-2'-propenyl)-3-amino-6-paramethoxy-phenyl-pyr idazinium bromide]. The results are compatible with the presence in the rat cerebral cortex of autoreceptors mediating inhibition of GABA release and belonging to the GABAB type. These autoreceptors may be activated tonically under physiological conditions.
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PMID:Release of gamma-[3H]aminobutyric acid (GABA) from electrically stimulated rat cortical slices and its modulation by GABAB autoreceptors. 254 42

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.
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PMID:GABAergic drugs and lordosis behavior in the female rat. 255 11

We carried out the forced swimming test in mice to investigate the antidepressant potentials of GABA transaminase (GABA-T) inhibitors including aminooxyacetic acid, ethanolamine-O-sulfate, gamma-vinyl GABA (GVG) and valproic acid (VPA). In acute experiments only GVG reduced immobility. Following chronic oral administration via drinking water containing the drugs, immobility was significantly reduced at days 5 and 10 in all of the GABA-T inhibitors examined. The tolerance of the anti-immobility effect, however, occurred at day 20. Brain GABA contents showed moderate to marked increase during the session with the exception of VPA, which did not alter GABA contents. These results suggest that subchronic GABA-T inhibitors possess antidepressant properties, though the anti-immobility effect of GABA-T inhibitors did not directly correlate with the increase in brain GABA.
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PMID:Potential antidepressant properties of subchronic GABA transaminase inhibitors in the forced swimming test in mice. 255 61

The hypothetical modulation by GABAergic neurons of yawning behavior in the rat was explored with GABA-active drugs. Gamma-acetylenic-GABA, a specific inhibitor of GABA-T, increases yawning frequency when injected at a dose of 7 mg/kg. Baclofen, a GABAB agonist (3 mg/kg), inhibits yawning completely; GABA antagonists, bicuculline and picrotoxin, at subconvulsant doses, also decrease yawning. All drugs were injected intraperitoneally with the exception of apomorphine, which was injected subcutaneously. It is suggested that GABAB receptors play a role in yawning behavior by modulating ACh release, and that GABAA receptors may modify yawning frequency by modulating inhibitory influences on ACh neurons.
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PMID:GABAergic modulation of yawning behavior. 256 Feb 2

In astrocytes grown in primary cultures from cerebral cortex of neonatal rats, alpha 1-adrenoceptors regulate the active uptake of glutamate followed by an activation of glutamic oxaloacetate transaminase (GOT; EC 2.6.1.1.) and a slight activation of glutamine synthetase (GS; EC 6.3.1.2.) activity. The beta-adrenoceptors regulate the active uptake of GABA, and this is followed by an activation of gamma-aminobutyric acid alpha-ketoglutarate transaminase (GABA-T; EC 2.6.1.19.). The data suggest that astrocyte adrenoceptors may modulate neurotransmitter induced neuronal excitability.
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PMID:Regulation of glutamate and GABA transport by adrenoceptors in primary astroglial cell cultures. 256 1


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