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)

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

An isocratic high-performance liquid chromatographic technique was developed to measure levels of gamma-aminobutyric acid (GABA), glutamate, and taurine in the brain and pituitary of goldfish. Accuracy of this procedure for quantification of these compounds was established by evaluating anesthetic and postmortem effects and by selectively manipulating GABA concentrations by intraperitoneal administration of the glutamic acid decarboxylase (GAD) inhibitor 3-mercaptopropionic acid or the GABA transaminase inhibitor gamma-vinyl GABA. The technique provided a simple, rapid, and reliable method for evaluating the concentrations of these amino acids without the use of complex gradient chromatographic systems. To investigate the relationship between neurotransmitter amino acids and the control of pituitary secretion of gonadotropin, the effects of injection of taurine, GABA, or monosodium glutamate on GABA, glutamate, taurine, and, in some instances, monoamine concentrations in the brain and pituitary were evaluated and related to serum gonadotropin levels. Injection of taurine caused an elevation in serum gonadotropin concentrations. In addition, injection of the taurine precursor hypotaurine but not the taurine catabolite isethionic acid elevated serum gonadotropin levels. Intracerebroventricular injection of either GABA or taurine also elevated serum gonadotropin concentrations. Pretreatment of recrudescent fish with alpha-methyl-p-tyrosine reduced pituitary dopamine concentrations and also potentiated the serum gonadotropin response to taurine. Injection of monosodium glutamate caused an increase of glutamate content in the pituitary at 24 h; this was followed by a decrease at 72 h after administration. Pituitary GABA, taurine, and dopamine concentrations underwent a transient depletion after monosodium glutamate administration, and this was associated with an elevation of serum gonadotropin content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid neurotransmitters and dopamine in brain and pituitary of the goldfish: involvement in the regulation of gonadotropin secretion. 134 46

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

In this study differences in the biochemical properties of 4-aminobutyric acid aminotransferase (GABA-T) from forebrain and cerebellum were detected. These differences may be related to: a) the characteristics of the catalytic site, b) the substrate affinities and c) their pyridoxal-phosphate requirements which suggests that PLP could be a physiological regulator of these forms of brain GABA-T.
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PMID:Comparative study between 4-aminobutyrate-2-oxoglutarate aminotransferase (GABA-T) from rat forebrain and cerebellum. 140 67

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

gamma-Vinyl GABA (GVG, vigabatrin) is a GABA transaminase-inhibiting antiepileptic agent. In dogs, chronic GVG administration produces reversible microvacuolation (intramyelinic edema) in discrete brain regions and slowing in central afferent transmission as measured by somatosensory evoked potentials (SEPs). Because this microvacuolation is especially prominent in the optic tract, this study tested the sensitivity of visual evoked potentials (VEPs) to GVG-induced changes in conduction. We also replicated the earlier SEP findings. Eight beagles received daily oral vigabatrin at the maximum tolerated dose (300 mg/kg/day); four were placebo controls. Cortical VEPs and SEPs were recorded using scalp needle electrodes at baseline and every 2 weeks throughout treatment. One treatment dog died at 2 weeks. The remainder showed an increase in central latencies beginning at 6 weeks, attaining significance (p < 0.05) at 8 and 10 weeks for SEPs and VEPs, respectively. No changes occurred in peripheral or spinal conduction in treated dogs, or in any measure in control dogs. Three GVG and two control dogs were followed after drug was withdrawn; both VEP and SEP measures returned to baseline values within 5 weeks. These findings support the use of VEPs and SEPs to monitor patients receiving vigabatrin therapy.
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PMID:Effects of high-dose gamma-vinyl GABA (vigabatrin) administration on visual and somatosensory evoked potentials in dogs. 142 96

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.
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PMID:Activation of D1 receptors stimulates accumulation of gamma-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats. 146 65

The acute effects of the irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor, gamma-vinyl GABA (Vigabatrin), were studied in the central nervous system of the rat. GABA concentrations were monitored in the hippocampus by implantation of microdialysis probes. Two doses of gamma-vinyl GABA (1.6 and 8.0 mM) were administered via the probes and were found to cause a transient increase in the basal GABA outflow (10-fold) during the period of drug administration. In addition, gamma-vinyl GABA pretreatment (1.6 mM) seemed to decrease K(+)-evoked GABA release (P < 0.05). The immediate increase of GABA outflow after gamma-vinyl GABA administration may be the result of direct blockade of GABA uptake sites, a finding which further indicates that the action of GABA transaminase inhibitors may be mediated partly through GABA uptake inhibition.
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PMID:Acute effects of gamma-vinyl GABA on the GABAergic system in rats as studied by microdialysis. 149 May 26


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