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 mice, tonic convulsive seizure induced by intravenous administration of caffeine (adenosine A1, A2 receptors antagonist) was significantly potentiated by any one of L-PIA (adenosine A1 receptor agonist), NECA (adenosine A2 receptor agonist) and 2-ClAd (adenosine A1, A2 receptors agonist). The caffeine-induced seizure was unaffected by diazepam (benzodiazepine receptor agonist), but was inhibited by Ro 15-1788 (antagonist or partial agonist). beta-DMCM (antagonist or inverse agonist) increased the seizure. Muscimol (GABA-a receptor agonist), baclofen (GABA-b receptor agonist) and AOAA (GABA transaminase inhibitor) did not show significant effect on caffeine-induced convulsion. Bicuculline (GABA-a receptor antagonist) and picrotoxin (chloride channel blocker) significantly potentiated the convulsion at the doses which did not induce it. Caffeine-induced convulsion was potentiated by NMDA with its non-convulsive dose. CPP (competitive NMDA receptor antagonist) and MK-801 (non-competitive NMDA receptor antagonist) significantly inhibited the seizures. These results suggest that caffeine-induced seizure is not caused by blockade of adenosine receptors. Caffeine may act to beta-carboline sensitive benzodiazepine receptor (Type 1) which has no linkage with GABA-a receptor. Furthermore, it is implied that caffeine plays some role at NMDA receptor calcium ion channel complex.
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PMID:[Effects of agonists and antagonists of benzodiazepine, GABA and NMDA receptors, on caffeine-induced seizures in mice]. 132 1

Quantitative histochemistry (scanning microphotometry) was used to determine the activities of the mitochondrial enzymes NAD-linked isocitrate dehydrogenase (EC 1.1.1.41), L-glutamate dehydrogenase (EC 1.4.1.3) and GABA transaminase (EC 2.6.1.19) in various layers of the hippocampus (middle one third) of young (3-4 months old) and memory-impaired aged rats (28-30 months old). For comparison, determinations of cytochrome c oxidase (EC 1.9.3.1) as a marker for mitochondria and energy metabolism were also performed. The study showed that there was a layered reaction pattern in the hippocampus and that the cellular distribution and the levels of enzyme activity were different. However, the activities of the different enzymes (excepting GABA transaminase and cytochrome c oxidase) were significantly correlated in the hippocampus in both age groups. Age-dependent changes were only observed for NAD-linked isocitrate dehydrogenase and GABA transaminase (significant increases of activities in some layers of the hippocampus, preferentially in the terminal field of the perforant path). From the present study it is concluded that, 1. the enzymatic complement of mitochondria in neurons and glia depends upon layer specific metabolic processes of the hippocampus (also with respect to glutamatergic and GABAergic terminal fields) indicating a layer specific interaction of the enzymes studied to produce or catabolize glutamate and GABA, and 2. the age dependent changes of the studied enzymes are very restricted.
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PMID:Mitochondrial enzymes related to glutamate and GABA metabolism in the hippocampus of young and aged rats: a quantitative histochemical study. 134 64

Extensive neuroanatomical, neurophysiological, and behavioral evidence demonstrates that GABAergic neurons inhibit endogenous dopamine release in the mammalian corpus striatum. Positron emission tomography (PET) studies in adult female baboons, using the dopamine D2-specific radiotracer 11C-raclopride, were undertaken to assess the utility of this imaging technique for measuring these dynamic interactions in vivo. 11C-raclopride binding was imaged prior to and following the administration of either gamma-vinyl-GABA (GVG), a specific suicide inhibitor of the GABA-catabolizing enzyme GABA transaminase, or lorazepam, a clinically prescribed benzodiazepine agonist. Striatal 11C-raclopride binding increased following both GVG and lorazepam administration. This increase exceeded the test/retest variability of 11C-raclopride binding observed in the same animals. These findings confirm that changes in endogenous dopamine concentrations resulting from drug-induced potentiation of GABAergic transmission can be measured with PET and 11C-raclopride. Finally, this new strategy for noninvasively evaluating the functional integrity of neurophysiologically linked transmitter systems with PET supports its use as an approach for assessing the multiple mechanisms of drug action and their consequences in the human brain.
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PMID:GABAergic inhibition of endogenous dopamine release measured in vivo with 11C-raclopride and positron emission tomography. 135 14

tau-Vinyl GABA (vigabatrin, GVG) is a novel antiepileptic drug that irreversibly inhibits GABA transaminase and elevates GABA levels in all parts of the brain. In the present study, we investigated the anxiolytic and behavioral effects of GVG in the elevated plus-maze and the hole board compared to diazepam. Doses of 500 and 1,000 mg/kg GVG were injected IP to different groups of male Wistar rats and animals were tested either 4 or 24 h after injection. Animals administered diazepam (1.5 mg/kg, IP) and saline (1 ml) were tested 20 min after injection. GVG and diazepam were found to decrease significantly the number of squares visited and rearing; both had a suppressant effect on locomotor activity. Neither drug had an effect on exploration (head dipping). GVG at a dose of 1,000 mg/kg was shown to have a similar anxiolytic activity either after 4 or 24 h as diazepam, while GVG at 500 mg/kg did not show any significant anxiolytic effect.
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PMID:Vigabatrin has an anxiolytic effect in the elevated plus-maze test of anxiety. 135 80

Multiple administrations of the psychotomimetic drug, phencyclidine-HCI (PCP), decreased striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels in a dose-dependent manner. Single or multiple PCP administrations decreased striatal NPY levels after 10-12 h; levels returned to control 24 h after a single dose or 58 h after multiple doses. In contrast, no significant changes were seen in nigral NPY levels with either acute or multiple-dose PCP treatments. The role of monoamine, sigma or opioid receptors in PCP-induced striatal NPY changes was evaluated. When administered alone, the alpha 1-adrenergic antagonist, prazosin, the sigma antagonist, BMY 14802, and the dopamine D2 antagonist, sulpiride decreased striatal NPY levels; however, only prazosin and the dopamine D1 antagonist, SCH 23390, significantly attenuated PCP-induced changes. Administration of the gamma-aminobutyric acid transaminase (GABA-T) inhibitors, amino-oxyacetic acid (AOAA) or gamma-vinyl-GABA (GVG, vigabatrin, MDL 71,754) alone had no effect on striatal NPY-LI levels while administration of these indirect GABA agonists prior to or concurrently with PCP treatment completely blocked PCP-induced changes in striatal NPY-LI levels. The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, on striatal NPY-LI content resembled that of PCP and was also blocked by the two indirect GABA agonists. These data suggest that NPY systems are modulated by glutamatergic activity (specifically by the NMDA receptor) and that the interaction between these two transmitter systems is mediated by GABAergic mechanisms.
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PMID:Characterization of phencyclidine-induced effects on neuropeptide Y systems in the rat caudate-putamen. 136 Aug 68

Long-term effects of chronic treatment with a GABA-T (GABA-transaminase) inhibitor, ethanolamine O-sulphate (EOS) (200 mg/kg/day for the postnatal days 3-21) on the binding parameters of GABAA receptors, hypothalamic monoamines and subsequent behavior were studied in Wistar rats. At the age of 1 month, EOS-treated rats showed reduced activity in the open-field and, at the age of 4 months, their voluntary alcohol consumption was increased. No changes were seen in Porsolt's swim test or in the plus-maze test. Weight gain was significantly retarded in EOS-treated rats. Maximal stimulation of [3H] flunitrazepam binding by GABA was decreased in the cerebral cortex and the EC50-value for the GABA stimulation increased in the hippocampus in the EOS rats at the age of 4 months. EOS treatment did not alter the cerebellar diazepam sensitive and insensitive binding components of the imidazobenzodiazepine [3H]Ro 15-4513. No changes were observed in the hypothalamic monoamine concentrations. The results are in agreement with the idea that GABA-T inhibitor treatment permanently alters GABAA mechanisms. Moreover, altering the CNS GABA level during development increases adult alcohol intake in rat.
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PMID:Neonatal administration of a GABA-T inhibitor alters central GABAA receptor mechanisms and alcohol drinking in adult rats. 136 55

1. The maternal to foetal transfers of S(+)- and R(-)-gamma-vinyl-GABA (VGB) across the human isolated perfused placenta were low and comparable with those of acidic alpha-amino acids. 2. The placental uptake of the active S(+)-isomer from the maternal circulation exceeded that of the R(-)-isomer and this was reflected by a corresponding difference in placental tissue concentrations. 3. During perfusion with recirculation of the foetal medium, the two enantiomers were present at a similar concentration and did not concentrate in foetal perfusate, indicating that the excess amount of S(+)-VGB cleared from the maternal circulation was not accessible to the foetal perfusate. Furthermore, stable concentrations of both isomers in the foetal perfusate suggested a lack of placental metabolism. 4. Possible explanations of these findings include the operation of a stereoselective sodium-dependent-GABA placental uptake system on the maternal side, similar to that observed in neuronal tissue, or stereoselective binding to a placental GABA transaminase.
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PMID:Passage of S(+) and R(-) gamma-vinyl-GABA across the human isolated perfused placenta. 141 75

The influence of GABA on pituitary gonadotrophin (GTH) release in the goldfish was studied by means of in vivo and in vitro techniques. It was found that GABA injected intraperitoneally caused an increase of serum GTH levels in regressed or early maturing fish, but not in late maturing animals. Moreover, injection of a GABA transaminase inhibitor caused a significant increase of GABA within the hypothalamus and pituitary, and a dose-dependent increase in serum GTH levels. To determine if this effect could be exerted directly at the level of the pituitary, dispersed pituitary cells in static incubation or in perifusion were exposed to increasing concentrations of GABA or its agonists muscimol and baclofen. None of these drugs was able to modify the spontaneous or GnRH-induced secretion of GTH, indicating that the in vivo effect of GABA was most likely mediated via another hypothalamic factor. Using in vitro incubation of pituitary slices, it was found that GABA caused a dose-related stimulation of GnRH release at the level of the pituitary, providing a possible explanation for the observed in vivo stimulatory effect of GABA on GTH release. Since the seasonal effect of GABA in vivo indicated a possible interaction of GABA with sexual steroids, GABA was given intraperitoneally to female goldfish implanted with either testosterone or estradiol. We found that the stimulatory effect of GABA on GTH release was abolished in estradiol-treated females but was still observed in testosterone-implanted fish. Moreover, estradiol but not testosterone caused a decrease of the GABA concentration within the telencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of GABA on gonadotrophin release in the goldfish. 156 6

Vigabatrin and (S)-4-allenylGABA (MDL 72483), two anticonvulsant GABA-T inhibitors, partially antagonize phencyclidine (PCP)-induced hyperactivity in mice at doses that do not affect spontaneous motor activity. The PCP antagonism is related to whole-brain GABA concentrations. The results indicate the potential use of GABA-T inhibitors in the therapy of PCP intoxications and perhaps also in the treatment of certain forms of endogenous psychoses.
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PMID:Antagonism of phencyclidine-induced hyperactivity in mice by elevated brain GABA concentrations. 158 40

The anticonvulsant, adverse and biochemical effects of the novel antiepileptic drug vigabatrin (gamma-vinyl GABA), which increases GABA (gamma-aminobutyric acid) levels by inhibition of the GABA degrading enzyme GABA aminotransferase, were examined in amygdala-kindled rats after acute and chronic administration. Vigabatrin proved to be a potent anticonvulsant drug at acute doses (100-200 mg/kg), but during chronic administration, the anticonvulsant activity of the treatment was lost already in the second week of treatment. Tolerance also developed to the adverse effects, i.e. hypothermia, sedation and motor impairment. Determination of vigabatrin in plasma indicated that tolerance was not due to declining drug levels. Furthermore, determination of endogenous amino acids in plasma showed that GABA levels were highly elevated throughout the period of treatment, although the extent of GABA accumulation decreased in the second week. After cessation of chronic treatment with vigabatrin, there was no clear indication of withdrawal symptoms, except a prolonged seizure or afterdischarge duration in experiments with 100 mg/kg per day. The data suggest that chronic treatment with vigabatrin may be associated with a loss of anticonvulsant efficacy, at least when the drug is given as monotherapy.
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PMID:Development of tolerance to the anticonvulsant effect of vigabatrin in amygdala-kindled rats. 161 78


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