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 the belief that homocysteine-induced convulsions might be related to alterations in brain gamma-aminobutyric acid metabolism, we have studied the action of this amino acid on the activity of glutamic decarboxylase (GAD, EC 4.1.1.15) and gamma-aminobutyrate aminotransferase (EC 2.6.1.19) of mouse brain in vitro DL-homocysteine competitively inhibited GAD with respect to both L-glutamate and pyridoxal 5'-phosphate. The respective Ki's were 3.8 mM and 0.3 mM. The activity of GABA-T also was altered in the presence of DL-homocysteine. A competitive inhibition (Ki = 6 mM) was observed with gamma-aminobutyric acid, and an uncompetitive inhibition with respect to pyridoxal 5'-phosphate and alpha-ketoglutarate. These results are explained in terms of a dual action of homocysteine on each of the enzymes: one involving a competition for substrate binding site and the other involving the formation of an inactive inhibitor-cofactor complex. The significance of the inhibition of these enzymes of gamma-aminobutyric acid metabolism is discussed in relation to the convulsant action of homocysteine.
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PMID:The mode of action of homocysteine on mouse brain glutamic decarboxylase and gamma-aminobutyrate aminotransferase. 90 1

The intramuscular administration of L-alpha-amino-beta-chloropropinonic acid hydroxamide (2 mmol/kg) to mice strongly inhibited the activity of GABA-T, but not GAD, in the brain of the animals. Adminstration of the compound 3 h prior to isonicotinic acid hydrazide treatment significantly delayed the onset of seizures induced by the hydrazide.
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PMID:L-alpha-amino-beta-chloropropionic acid hydroxamide: an inhibitor of GABA-lapha-oxoglutarate aminotrarsferase. 95 28

The regional distribution of 9 amino acids, including glutamate and GABA and their metabolising enzymes, has been determined in 5 regions of the frog CNS. Glycine was relatively concentrated in the spinal cord whereas the highest concentration of each of the other amino acids was found in the midbrain. There was a good correlation between the activity of l-glutamate-1-carboxylase (GAD) and the level of GABA in all regions examined and both were concentrated in the midbrain. There was little regional variation in the distribution of 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T).
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PMID:Glutamic acid, GABA and their metabolising enzymes in the frog central nervous system. 107 86

C57BL/10Bg sps/sps mice display behavioral arrest, similar to generalized absence seizures. Compared with the parent strain C57BL/10Bg SPS/SPS, the activities of glutamate decarboxylase (GAD, E. C. 2.6.1.15), GABA aminotransferase (GABA-T, E. C. 2.6.1.19), aspartate aminotransferase (ASP-T, E. C. 2.6.1.1), and glutamate dehydrogenase (GDH, E. C. 1.4.1.3) in whole brain crude supernatant were significantly reduced in the sps/sps mice. Alanine aminotransferase activity (ALA-T, E. C. 2.6.1.2), was not altered in any of the strains, and normalization of GAD, GABA-T and GDH activities by that of ALA-T, further revealed significant differences between the normal strain (SPS/SPS), the heterozygotes (SPS/sps), and behavioral arrest (sps/sps) mice. These results suggest the possible involvement of GABAergic and glutamatergic neurotransmission in the absence-like behavior displayed by sps/sps mice. Open field behavior of C57BL/10Bg sps/sps mice is characterized by periods of marked inactivity which easily distinguish affected homozygotes, from their heterozygotes littermates.
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PMID:The C57BL/10Bg sps/sps mouse: a mutant with absence-like seizures; neurochemical and behavioral correlates. 239 34

The technique of estimating gamma-aminobutyric acid (GABA) turnover by inhibiting its major degrading enzyme GABA-T (4-aminobutyrate:2-oxoglutarate aminotransferase; EC 2.6.1.19) and measuring GABA accumulation has been used repeatedly, but, at least in rats, its usefulness has been limited by several difficulties, including marked differences in the degree of GABA-T inhibition in different brain regions after systemic injection of GABA-T inhibitors. In an attempt to improve this type of approach for measuring GABA turnover, the time course of GABA-T inhibition and accumulation of GABA in 12 regions of rat brain has been studied after systemic administration of aminooxyacetic acid (AOAA), injected at various doses and with different routes of administration. A total and rapidly occurring inhibition of GABA-T in all regions was obtained with intraperitoneal injection of 100 mg/kg AOAA, whereas after lower doses, marked regional differences in the degree of GABA-T inhibition were found, thus leading to underestimation of GABA synthesis rates, e.g., in substantia nigra. The activity of the GABA-synthesizing enzyme GAD (L-glutamate-1-decarboxylase; EC 4.1.1.15) was not reduced significantly at any time after intraperitoneal injection of AOAA, except for a small decrease in olfactory bulbs. Even the highest dose of AOAA tested (100 mg/kg) was not associated with toxicity in rats, but induced motor impairment, which was obviously related to the marked GABA accumulation found with this dose. The increase in GABA concentrations induced with intraperitoneal injection of 100 mg/kg AOAA was rapid in onset, allowing one to estimate GABA turnover rates from the initial rate of GABA accumulation, i.e., during the first 30 min after AOAA injection. GABA turnover rates thus determined were correlated in a highly significant fashion with the GAD activities determined in brain regions, with highest turnover rates measured in substantia nigra, hypothalamus, olfactory bulb, and tectum. Pretreatment of rats with diazepam, 5 mg/kg i.p., 5-30 min prior to AOAA, reduced the AOAA-induced GABA accumulation in all 12 regions examined, most probably as a result of potentiation of postsynaptic GABA function. The data indicate that AOAA is a valuable tool for regional GABA turnover studies in rats, provided the GABA-T inhibitor is administered in sufficiently high doses to obtain complete inhibition of GABA degradation.
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PMID:Use of inhibitors of gamma-aminobutyric acid (GABA) transaminase for the estimation of GABA turnover in various brain regions of rats: a reevaluation of aminooxyacetic acid. 280 89

Postmortem changes in the activity of GDH, GAD, GABA-T, and GS in the adult forebrain and cerebellum and in the forebrain of newborns have been investigated. The activities of GDH, GAD, and GS were stable till 12 hr after death in both adult and young brain regions studied. The activity of GABA-T was stable till 30 min postmortem, but declined progressively thereafter in both regions in adult, as well as in young forebrain.
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PMID:Postmortem changes in the enzymes of GABA and glutamate metabolism in the cerebellum and forebrain of newborn and adult rats. 287 80

The acute effects of corticosterone (0.5 and 1 mg/kg, i.p.) upon the GABAergic system have been investigated. While no changes were detected after treatment with corticosterone 0.5 mg/kg, the administration of 1 mg/kg lowered the levels of gamma-aminobutyric acid (GABA) (29%) in the mediobasal hypothalamus either 30 or 60 min after injection in both young (3-4 weeks old) and adult (7-8 weeks old) rats. No changes were found in the frontal cerebral cortex. Only in young rats did the administration of corticosterone (1 mg/kg, 30 min) reduced GABA levels in the corpus striatum (34%). In young rats this dose of corticosterone: 1. did not affect the activity of the enzymes of the metabolism of GABA (GAD and GABA-T); 2. reduced neuronal 3H-GABA uptake in the corpus striatum (30%) and in the mediobasal hypothalamus (46%), and increased it in the frontal cortex (2-fold); 3. enhanced the turnover of GABA (2-fold) in the corpus striatum. These values were unaffected by 0.5 mg/kg. Corticosterone 0.5 and 1 mg/kg did not alter non-neuronal 3H-GABA uptake. These findings show an area-related and age- and dose-dependent response of the GABAergic pathways to acute corticosterone treatment. This is discussed in relation to the age-related sensitivity to the environmental stimuli which cause this release of corticosteroids. The stimulation of GABAergic function which occurs mainly in the corpus striatum as estimated from the increase in its turnover may be related to the postulated anticonvulsant role of corticosteroids.
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PMID:Changes in the central GABAergic system after acute treatment with corticosterone. 321

Acute exposure of adult male albino rats (110-120 g) to higher environmental temperature (40 +/- 1 degrees C) increased body temperature (BT). This increase of BT was also dependent on the duration of exposure. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia at room temperature (28 +/- 1 degree C) and resistance to increase the body temperature when exposed to higher temperature (40 +/- 1 degree C). Administration of bicuculline (1 mg/kg, i.p.), a GABA antagonist, on the other hand, enhanced BT more than that observed in control (normal) rat exposed to higher temperature (40 +/- 1 degree C), although at room temperature bicuculline treatment did not show any effect on BT. Pretreatment with ethanolamine-O-sulfate (EOS) (2 g/kg, s.c.), a GABA transaminase inhibitor, to rats exposed to higher temperature increased BT as in control (normal) rat. Inhibition of central GAD activity with mercaptopropionic acid (MPA) (70 mg/kg, i.p.) produced resistance to increase BT during its period of action when rats were exposed to higher environmental temperature (28 +/- 1 degree C). These results thus suggest that central inhibitory neuron, GABA, plays a regulatory role in thermoregulation.
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PMID:Involvement of GABA in environmental temperature-induced change in body temperature. 323 43

It has been reported that thyrotropin-releasing hormone (TRH) improves the ataxia of cerebellar type. The mechanism of action is unclear. As well recognized, GABA (gamma aminobutyric acid) is an important neurotransmitter in cerebellar system. So, if TRH acts on cerebellum, it is expected that the GABA metabolism will be modified by in vivo or in vitro TRH application. The purpose of this experiment is to clarify whether or not TRH affects on GABA system in cerebellar system. The first experiment was to determine the effect of TRH on the two GABA related enzyme activities, that is, GAD (glutamic acid decarboxylase) and GABA-T (GABA-transaminase). TRH was intraperitoneally injected at a dose of 5 mg/kg. In mouse brains, the two enzyme activities of hindbrains increased after 60 minutes. Next experiment assaying GAD activities at two parts of hindbrain revealed that the increase in hindbrain observed above was due to marked increase in brain-stem (p less than 0.001), but not in cerebellum itself in which the GAD activities decreased (p less than 0.05). On the other hand, in the forebrains, the same dose of TRH failed to change both GAD and GABA-T activities. In order to ascertain the effect more precisely, we assayed GAD activities at seven parts of the brain of Wistar male rats. By this experiment, it was found that GAD activities increase at two portions, namely, at thalamo-midbrain after 30 minutes and at pons-medulla after 180 minutes of TRH injection (p less than 0.05, in both). Other five portions, including cerebellum, showed no significant change of GAD activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of thyrotropin releasing hormone (TRH) on GABA (gamma aminobutyric acid) metabolism in mouse and rat brains: as to the activities of GAD (glutamic acid decarboxylase), GABA-T (GABA-transaminase) and GABA re-uptake]. 393 48

Subcutaneous administration of high doses of glutamate to rats during their first 10 days after birth produced a great reduction of GABA content and GAD activity in the adult mediobasal hypothalamus, both in male and female. In addition GABA content and GAD activity showed a slight significant decrease in female cerebellum and male striatum. Glutamate treatment was also followed by a significant increase in GABA content and GAD activity of male substantia nigra, cerebellum, hippocampus and of female olfactory bulb. No reduction in GABA-T activity was observed in different brain areas studied except in mediobasal hypothalamus. The results support the view that glutamate treatment had a direct toxic effect on GABA-ergic neurons in mediobasal hypothalamus. The changes in GAD activity observed in all areas studied may reflect the neuroendocrine changes determined by nucleus arcuate lesions.
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PMID:GABA-ergic system in brain regions of glutamate-lesioned rats. 400 30


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