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)

Pyritinol, a vitamin B6 derivative considered to have an activating effect on brain inhibited glutamate decarboxylase in concentrations of 0.05-1.0 mmol/l. This effect was not dependent on the pyridoxal-5'-phosphate concentration. An increase in the glutamate level reduced the inhibitory effect of pyritinol, but inhibition was not competitive. It is supposed that this modification of inhibition of glutamate decarboxylase by the substrate concentration might be associated with the presence of two glutamate decarboxylases with different affinities for the substrate. The inhibitory effect of pyritinol was dependent on integrity of the disulphide bond in the pyritinol molecule. Inhibition of glutamate decarboxylase increased in correlation to time--possibly in association with progressive oxidation of the SH-groups of the enzyme. Pyritinol did not influence GABA transaminase activity, but lessened the oxidation of GABA to carbon dioxide. It is assumed that succinic semialdehyde dehydrogenase activity was inhibited.
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PMID:Pyritinol and the enzymes of gamma-aminobutyric acid (GABA) synthesis and degradation. 297 3

Previous cytoarchitectural and electron micrographic studies have indicated that the gustatory zone of the nucleus of the solitary tract (NST) may contain local circuit neurons. It is known that neurons of the caudal "visceroceptive" NST contain GABA, glutamic acid decarboxylase (EC 4.1.1.15), and GABA-transaminase (GABA-T; 4-aminobutyrate: 2-oxoglutarate aminotransferase; EC 2.6.1.19). The present study was conducted to determine whether or not neurons in the gustatory zone of the NST of rat contain GABA and the principle degradative enzyme of GABA, GABA-T. Transganglionic transport of horseradish peroxidase (HRP) was used to identify chorda tympani (CT) nerve terminal fields. Immunohistochemical studies were combined with transport experiments to evaluate the organization of GABA immunoreactive neurons in CT terminal fields. Results show that GABA immunoreactive neurons and puncta are located within CT terminal fields. These neurons evince small ovoid morphologies resembling Golgi interneurons, and comprise an average of 18% of total neurons in CT terminal fields. Independent histochemical studies reveal that approximately 82% of GABA immunoreactive neurons within CT terminal fields exhibit GABA-T activity. Retrograde transport of HRP was used in additional studies to evaluate whether or not axons of putative GABAergic neurons project to the second-order central gustatory relay located in the caudal parabrachial nucleus (PBNc), to the caudal NST, or to regions surrounding the rostral or caudal NST. Combined studies indicate that GABA immunoreactive neurons in the gustatory NST do not project axons to the PBNc, to the caudal NST, or to regions adjacent to the rostral or caudal NST.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Organization of GABA and GABA-transaminase containing neurons in the gustatory zone of the nucleus of the solitary tract. 320 50

Hepatic coma was induced in rats chronically treated with CCl4, by means of a single injection of ammonium acetate. The activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), as well as the synaptosomal uptake and release of [3H]GABA, were measured in the following brain areas of the comatose rats: cortex, striatum, hypothalamus, hippocampus, midbrain and cerebellum. Hepatic coma was associated with a general decrease of GAD activity, whereas GABA-T activity was diminished only in the hypothalamus, striatum and midbrain. During hepatic coma, the K+-stimulated [3H]GABA release was notably diminished in the striatum and cerebellum, whereas a significant increase was observed in the hippocampus. [3H]GABA uptake increased in most regions after CCl4 treatment, independently of the presence of coma. The results indicate that GABAergic transmission seems to be decreased in most cerebral regions during hepatic coma.
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PMID:Regional brain GABA metabolism and release during hepatic coma produced in rats chronically treated with carbon tetrachloride. 336 28

Pilocarpine, given intraperitoneally to rats, reproduces the neuropathological sequelae of temporal lobe epilepsy and provides a relevant animal model for studying mechanisms of buildup of convulsive activity and pathways operative in the generalization and propagation of seizures within the forebrain. In the present study, the effects of manipulating the activity of the gamma-aminobutyric acid (GABA)-mediated synaptic inhibition within the substantia nigra on seizures produced by pilocarpine in rats, were investigated. In animals pretreated with microinjections of isoniazid, 150 micrograms, an inhibitor of activity of the GABA-synthesizing enzyme, L-glutamic acid decarboxylase, into the substantia nigra pars reticulata (SNR), bilaterally, non-convulsant doses of pilocarpine, 100 and 200 mg/kg, resulted in severe motor limbic seizures and status epilepticus. Electroencephalographic and behavioral monitoring revealed a profound reduction of the threshold for pilocarpine-induced convulsions. Morphological analysis of frontal forebrain sections with light microscopy revealed seizure-related damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex, which is typically observed with pilocarpine in doses exceeding 350 mg/kg. Bilateral intrastriatal injections of isoniazid did not augment seizures produced by pilocarpine, 200 mg/kg. Application of an irreversible inhibitor of GABA transaminase, gamma-vinyl-GABA (D,L-4-amino-hex-5-enoic acid), 5 micrograms, into the SNR, bilaterally, suppressed the appearance of electrographic and behavioral seizures produced by pilocarpine, 380 mg/kg. This treatment was also sufficient to protect animals from the occurrence of brain damage. Microinjections of gamma-vinyl-GABA, 5 micrograms, into the dorsal striatum, bilaterally, failed to prevent the development of convulsions produced by pilocarpine, 380 mg/kg. The results demonstrate that the threshold for pilocarpine-induced seizures in rats is subjected to the regulation of the GABA-mediated synaptic inhibition within the substantia nigra.
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PMID:Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma-vinyl-GABA into the substantia nigra. 370 28

Four inhibitors of gamma-aminobutyric acid transaminase (GABA-T) were investigated together with respect to their effects on hole-board exploration and temperature and the relation with effects on quasi-morphine-abstinence behaviour induced by dipropylacetate (DPA) in rats. Amino-oxyacetic acid (AOAA), gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVC) and ethanolamine-O-sulfate (EOS) were found to reduce hole-board exploration especially in the higher doses used, although the time-course of the effect was different for the compounds. For EOS and GVG the decrease in hole-board exploration paralleled a strong hypothermic effect. The compounds AOAA and GAG exerted a less and more transient hypothermic effect. However, the decrease in hole-board exploration did not fall in with this decrease in temperature. AOAA and GAG were found to decrease DPA-induced body shakes and locomotor activity, while GVG and EOS had no effect on body shakes and transient effects but opposite to each other, on locomotor activity. The efficacy of the GABA-T-inhibitors was measured biochemically, and the influence on the activity of glutamate decarboxylase (GAD) was also determined. AOAA and GAG were found to be strong inhibitors of GABA-T whereas the other two compounds were less efficient in the used doses. In addition AOAA and GAG influenced the activity of GAD strongly, while using GVG only a small decrease was found. The results suggest that the anti-quasi-withdrawal, the sedative and the hypothermic effects are not related to each other nor related to an effect on GABA-T. The suppressive effects on quasi-withdrawal body shakes, however, could be related to the inhibition of GAD and a hypothesis involving a compartmentalized action of DPA on GABA-metabolism has been proposed.
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PMID:Effects of inhibitors of GABA-transaminase on hole-board exploration and on temperature. Relation with effects on quasi-morphine abstinence behaviour induced by sodium dipropylacetate. 393 14

The concentrations of GABA, glutamate, serine, glutamine, threonine, glycine and taurine in the substantia nigra and in the corpus striatum of the rat were determined electrochemically following condensation with o-phthalaldehyde-beta-mercaptoethanol and reverse-phase, high performance liquid chromatography. After a frontal hemisection at the level of the caudal hypothalamus, the GABA concentration in the substantia nigra on the operated side decreased to about 20 per cent of the normal value in 4 days, in all probability caused by degeneration of the nerve terminals of the striato-nigral GABA neurons. The concentrations of taurine in the substantia nigra and of GABA in the corpus striatum were initially lowered and later elevated following this lesion. The concentration of glutamate in the substantia nigra was lower on the sectioned side and higher on the intact side at 14 days as compared to 4 hours after a hemisection. Following an acute hemisection, the GABA transaminase inhibitor gamma-acetylenic GABA increased the concentration of GABA by 36% and 79% in the substantia nigra on the sectioned and intact side, respectively. The glutamate decarboxylase inhibitors 4-deoxypyridoxine and isoniazid lowered the concentration of GABA in the substantia nigra by about 50% on both the sectioned and intact side. The results indicate that the synthesis, but not the utilization of GABA in the substantia nigra is dependent on the normal nerve impulse flow. The concentration of glutamine was changed in directions contrary to that of GABA following a chronic hemisection or treatment with gamma-acetylenic GABA, in agreement with the suggestion that glutamine is a precursor of the GABA transmitter pool.
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PMID:Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra. 398 Nov 61

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

Bilateral ablation of the olfactory bulbs caused marked changes in the 'turnover' of several neurotransmitters in the amygdaloid cortex and the mid-brain areas of the rat brain. Following tyrosine and tryptophan hydroxylase inhibition, the decrease in the concentration of noradrenaline and serotonin respectively in the amygdaloid cortex was not so marked in the bulbectomized rats as in their controls. This suggests that the 'turnover' of these biogenic amines is reduced following bulbectomy. Following GABA transaminase inhibition, the increase in the concentration of GABA in this region was increased compared to the controls thereby suggesting that the 'turnover' of the inhibitory neurotransmitter was enhanced, glutamate decarboxylase activity was also increased in the amygdaloid cortex. No changes were found in the 'turnover' of noradrenaline or serotonin in the mid-brain but that of dopamine was decreased as was the activity of glutamate decarboxylase. It is concluded that changes in neurotransmitter 'turnover' in these brain regions are attributable to the destruction of the olfactory bulbs and may contribute to the behavioural deficits which we, and others, have reported elsewhere.
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PMID:Changes in neurotransmitter metabolism following olfactory bulbectomy in the rat. 620 59

GABA transaminase activity is reduced in autopsied putamen samples from patients dying with Huntington's disease. Its activity is also reduced in the striatum of rats previously lesioned with kainic acid. In both cases, the reduction in GABA transaminase activity is comparable with the reduction in glutamate decarboxylase activity, supporting the suspected localization of this enzyme to GABA neurones within the basal ganglia.
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PMID:Reduced GABA transaminase activity in the Huntington's disease putamen. 623 80

Uptake, synthesis, storage, and release of gamma-aminobutyric acid (GABA) are some of the characteristic properties of GABA-ergic neurons. In the present study, we have used these properties as physiological probes to follow the emergence and maturation of GABA-ergic neurons during postnatal development of the rabbit retina. There is autoradiographic, immunocytochemical, and pharmacological evidence that some amacrine cells and certain neurons in the ganglion cell layer probably use GABA as the neurotransmitter. These neurons take up GABA, contain the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD, EC 4.1.1.15), and release the accumulated GABA by a CA++-dependent mechanism when depolorized with high extracellular K+ concentration. In this study, we show that certain neurons in the newborn retina already possess a specific mechanism for GABA uptake. The positions and numbers of these cells in the developing retina suggest that they will become GABA-ergic neurons in the adult retina. These putative GABA-ergic neurons are, however, probably immature at birth because newborn retinas contain only low levels of GABA and GAD. Additionally, there is relatively little K+-stimulated, Ca++-dependent release of (3H)-GABA from the newborn retinas. GABA concentrations and GAD activities in developing retinas increase steadily postnatally, reaching about 80% of the adult levels by day 9. The activities of the GABA-degrading enzyme, GABA-glutamate transaminase (GABA-T, EC 2.6.1.19), follow a similar pattern of maturation during retinal development. K+ stimulated GABA release, however, remains low until about day 6, and then increases dramatically from 20% to 85% of the adult level over the next 3 days. Taken together, our results indicate that in the rabbit retina, the commitment by certain neurons to use GABA as the transmitter is made prenatally. These neurons are immature at birth but are biochemically, physiologically, and probably functionally mature by about 9 days after birth.
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PMID:Postnatal development of GABA-ergic neurons in the rabbit retina. 625 33


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