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)

Alterations in gamma-aminobutyric acid (GABA) metabolism have been investigated in the kindling model of epilepsy. Numerous generalized seizures were induced by amygdala-kindling stimulations in rats. One week after the last stimulation, there were no changes in GABA levels nor in the activity of enzymes responsible for the synthesis (glutamic acid decarboxylase) and catabolism (GABA transaminase and succinyl semialdehyde dehydrogenase). These results do not exclude other changes in GABA function as modifications of transport or receptors.
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PMID:Absence of modifications in gamma-aminobutyric acid metabolism after repeated generalized seizures in amygdala-kindled rats. 408 36

1 The synthesis of two analogues of gamma-aminobutyric acid (GABA), beta-chloro GABA and beta-phenyl GABA is described.2 The activity of brain GABA aminotransferase was inhibited by beta-chloro GABA (5.7 x 10(-5)M) and beta-phenyl GABA (4.6 x 10(-3)M) in a competitive manner with GABA.3 beta-Chloro GABA exhibited 50% of the inhibitory activity of GABA in blocking the discharge of the crayfish stretch receptor neurone; beta-phenyl GABA had no detectable effect.4 Injection of beta-phenyl GABA (200 mg/kg) into normal or epileptic cats (cobalt) caused the appearance of synchronized slow-wave EEG activity.5 Administration of beta-chloro GABA (200 mg/kg) to epileptic cats (cobalt) produced a temporary diminution or abolition of epileptic discharges while causing no alteration in normal EEG activity.6 beta-Chloro GABA and beta-phenyl GABA had no effect on the concentrations of catecholamines or of amino acids in mouse brain.7 The results suggest that both beta-chloro GABA and beta-phenyl GABA may pass the blood-brain barrier.
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PMID:Biological actions in vivo and in vitro of two gamma-aminobutyric acid (GABA) analogues: beta-chloro GABA and beta-phenyl GABA. 415 85

1. Rat retinae pre-incubated and incubated at 37 degrees C in media containing amino-oxyacetic acid (AOAA) (0.1 muM to 1 mM) accumulated more (3)H-gamma-aminobutyric acid ((3)H-GABA) than control retinae incubated in the absence of AOAA. This increased accumulation of (3)H-GABA by tissue exposed to AOAA was not apparent at short incubation times (0-20 min), but became significant after incubations of 30 min, and maximal after incubation for 60 minutes.2. At a concentration of 10 muM, AOAA did not alter the apparent K(m) for (3)H-GABA uptake or V(max) for either the low or the high affinity GABA uptake systems present in retina.3. The potentiation of (3)H-GABA accumulation produced by AOAA appeared to parallel the inhibitory effect of this compound on 2-oxoglutarate-4-aminobutyrate aminotransferase (GABA-T). Similarly, hydrazinopropionic acid inhibited retinal GABA-T and potentiated the accumulation of (3)H-GABA, but hydroxylamine and thiosemicarbazide which did not affect GABA-T, were also without effect on the retinal accumulation of (3)H-GABA.4. In vitro incubation with AOAA did not increase the endogenous levels of GABA or other amino acids in the retina.5. AOAA did not significantly increase the retinal accumulation of radioactive L-glutamate, L-glutamine, taurine, glycine, alpha-aminoisobutyrate or dopamine: the accumulation of L-aspartate was increased by approximately 30%.6. The inhibition of retinal GABA-T by AOAA was time-dependent and was not reversed by pyridoxal-5'-phosphate or by repeated washing of the tissue with fresh medium.7. AOAA also inhibited glutamate decarboxylase (GAD) in retinae incubated in vitro. This inhibitory effect was partially reversed by pyridoxal-5'-phosphate.8. Efflux of radioactivity from the retina was strikingly reduced in the presence of AOAA at concentrations sufficient to inhibit GABA-T by 100%.9. These findings suggest that AOAA potentiates the accumulation of (3)H-GABA by isolated retina, not by increasing the exchange of (3)H-GABA with the endogenous GABA pools, but by reducing the metabolism of the amino acid and hence reducing the loss of radioactivity from the tissue in the form of tritiated metabolites.
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PMID:Effect of inhibitors of -aminobutyrate aminotransferase on the accumulation of 3H- -aminobutyric acid by the retina. 473 Aug 31

The influence of 2-(2-oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1, 1-dioxide (supidimide), a representative of a new class of sedative drugs, on the noradrenergic, dopaminergic, serotoninergic and gamma-aminobutyric acid (GABA)ergic neuronal systems of rodent brains was investigated. In each case the brain transmitter levels after administration of supidimide were determined. Utilisation of noradrenaline (norepinephrine, NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) was also investigated ex vivo. The study was complemented with in vitro investigations of biosynthesis, synaptosomal uptake, degradation, and receptor binding of the transmitters. Based on a preliminary study of the distribution of [35S]-supidimide in rat brain, in vitro effects observed at greater than 10(-4) mol/l were considered irrelevant. Similarly, in vivo effects requiring dosages higher than 300 mg/kg i.p. were not regarded adequate to explain the sedative and antiaggressive efficacy of supidimide. With the above restrictions, the following parameters can be rated as not influenced by supidimide: levels of tryptophan in rat brain and serum (free and total); 5-HT biosynthesis in vivo (rat brain; 5-HT accumulation after monoamine oxidase (MAO) blockade); activity of MAO-A and MAO-B (rat brain mitochondria); uptake of 5-HT, NE and DA (rat synaptosomes); 5-HT receptor binding ( [3H]-LSD binding assay in rat cortical membranes); tyrosine hydroxylase activity (rat adrenal glands); catechol-O-methyl transferase (COMT) (rat liver); NE binding to central alpha 1- and alpha 2-receptors (rat brain; radioligand assay with [3H]-dihydroergocryptine, [3H]-prazosin and [3H]-WB 4101 (2',6'-dimethoxy-(G-3H]-phenoxy]-ethylaminomethylbenzo-1,4-dioxane ); DA levels (whole rat brain and striata); dihydroxyphenylacetic acid (DOPAC) levels (whole rat brain without cerebellum and striata); elevated DOPAC levels after pretreatment with haloperidol; DA-dependent adenylate cyclase in vitro (rat striatum); D2 receptor binding ( [3H]-spiperone binding assay, rat striatum); GABA levels (mouse brain); GABA transaminase activity (mouse brain stem); sodium-independent [3H]-GABA receptor binding (rat brain) and benzodiazepine binding (rat cortical membranes, [3H]-diazepam binding assay). Two effects on the GABAergic system were induced by supidimide. Starting at 300 mg/kg i.p., supidimide slowed down the GABA accumulation in brains of aminooxyacetate-treated mice. At 10(-4) mol/l supidimide caused a significant inhibition of GABA uptake (rat synaptosomes).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of supidimide on brain neurotransmitter systems of rats and mice. 608 11

A pharmacohistochemical method for gamma-aminobutyric acid transaminase, the key enzyme for gamma-aminobutyric acid metabolism, has been combined with retrograde tracing by horseradish peroxidase, to a study of projections from the midbrain to the superior colliculus. The results indicate projections from the substantia nigra zona reticulata, the zona incerta and the reticular formation of the mesencephalon which are exclusively from neurons staining intensely for gamma-aminobutyric acid transaminase and presumptively gamma-aminobutyric acid as their transmitter. The projection from the ventral lateral geniculate body to the superior colliculus, on the other hand, comes from cells which do not stain for gamma-aminobutyric acid transaminase and therefore do probably not use gamma-aminobutyric acid as their transmitter.
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PMID:Presumptive gamma-aminobutyric acid pathways from the midbrain to the superior colliculus studied by a combined horseradish peroxidase-gamma-aminobutyric acid transaminase pharmacohistochemical method. 609 62

Brain gamma-aminobutyric acid (GABA) has been proposed to play a role in the modulation of extrapyramidal motor function. The effects of increasing brain GABA with gamma-acetylenic GABA (GAG), a drug that inhibits GABA transaminase, were evaluated in ten patients with stable tardive dyskinesia during a blind placebo-controlled trial. Drug effects during active treatment and two placebo periods were evaluated by scoring randomly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during a standardized examination. Tardive dyskinesia was significantly reduced, and preexisting parkinsonism increased slightly. The largest decrease in tardive dyskinesia symptoms occurred in patients receiving higher neuroleptic doses, suggesting an interaction between GABA and dopamine. Prolactin values increased but growth hormone values were unchanged. Psychiatric symptoms were also unchanged during GAG treatment.
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PMID:gamma-Acetylenic GABA in tardive dyskinesia. 610 51

A single high oral dose of 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2, 4-pyrimidinedione (FD-1) (486.0-729.0 mg/kg) followed by daily administration of lower doses of FD-1 (121.5 mg/kg) for 2-4 weeks increased the concentration of striatal dopamine (DA) in rats. The decrease in striatal DA following an injection of alpha-methyl-p-tyrosine methyl ester (alpha-MT) was lessened by a dose of FD-1 (364.8 mg/kg, p.o.) given immediately before the alpha-MT. This may indicate a decrease in striatal DA utilization by FD-1. The increase in striatal DA after FD-1 was inhibited by two antagonists of gamma-aminobutyric acid (GABA) which act on postsynaptic receptors: bicuculline (0.5-2.0 mg/kg, i.p.) and picrotoxin (2.0 mg/kg, i.p.). The increase of DA induced by the GABA transaminase inhibitor aminooxyacetic acid (AOAA) was enhanced by FD-1. These results suggest that the action of FD-1 is mediated by GABA. FD-1 probably causes inhibition of DA release from nerve terminals resulting in an accumulation of DA in the corpus striatum.
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PMID:Effects of 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinedione (FD 1) on the central nervous system: (2) Effects on nigro-striatal dopaminergic neurons. 611 4

gamma-Vinyl GABA (gamma-aminobutyric acid), a drug that increases brain GABA via GABA transaminase inhibition, was evaluated in a blind, placebo-controlled trial in 10 patients with stable tardive dyskinesia. Drug effects during active treatment (2 to 6 g/day) and during pre- and posttreatment placebo periods were determined by scoring randomly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during standardized examinations. Tardive dyskinesia was significantly reduced, and correlated to increased parkinsonism. Eye blinking rates decreased, but psychiatric symptoms were unchanged during treatment.
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PMID:Effect of gamma-vinyl GABA in tardive dyskinesia. 613 54

Metabolism of the glutamate group of amino acids--glutamic acid, gamma-amino-butyric acid, glutamine, aspartic acid and alanine--was studied in the brain of rat as a function of age. The levels of glutamic acid, glutamine and aspartic acid decreased while those of gamma-aminobutyric acid, and alanine increased with age. The results on the activity of the twelve enzymes involved in the metabolism showed that five of them (glutamate dehydrogenase, glutamine synthase, gamma-aminobutyric acid transaminase, succinic semialdehyde dehydrogenase and NAD+-isocitrate dehydrogenase) decreased, while four of them (glutaminase, glutamotransferase, glutamic acid decarboxylase, and alpha-ketoglutarate dehydrogenase) increased. The other three enzymes (aspartate aminotransferase, alanine aminotransferase and NADP+-isocitrate dehydrogenase) did not show any significant change in activity. An age-related increase was seen in alpha-ketoglutarate and ammonia, the intermediates involved in the metabolism of these amino acids. The changes in the level of these amino acids are discussed in relation to the altered energy metabolism during aging.
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PMID:Metabolism of the glutamate group of amino acids in rat brain as a function of age. 614 62

Four groups of rats were given free choice between water and solutions of either 3 micrograms/ml etonitazene, 5% ethanol (v/v), 0.1 mg/ml diazepam or 3 mg/ml barbital for 10-14 days. With the exception of barbital, some rats spontaneously preferred the drug solutions to water. This preference was reduced by addition of 7 micrograms/ml haolperidol. In a forced drug fluid consumption procedure, the daily administration of 15 mg/kg i.p. of the gamma-aminobutyric acid (GABA)-transaminase blocker aminooxyacetic acid (AOAA) led to a reduction of ethanol and diazepam intake, but not of etonitazene and barbital. It is suggested that the diminished consumption of ethanol and diazepam as caused by GABA-T-inhibition may also be mediated by dopamine which seems to act indirectly, via benzodiazepine receptors and GABA neurons.
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PMID:The influence of haloperidol and aminooxyacetic acid on etonitazene, alcohol, diazepam and barbital consumption. 615 Aug 37


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