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)

The RMI, an irreversible inhibitor of GABA transaminase, inhibited, at the dose of 100 mg/kg, the activity of Mice placed in an open-field. At lower doses, RMI improved the activity in open-field and the number of conditioned avoidance reactions. Results are correlated with increase of the level of brain GABA, following administration of RMI.
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PMID:[Effect of an irreversible inhibitor (RMI71645) of gamma-aminobutyric acid (GABA) transaminase on spontaneous and conditioned activities of mice]. 82 60

The knowledge that GABA is an inhibitory neurotransmitter substance in brain has spurred a prodigious research effort to implicate GABA in the etiology of seizures. Such an involvement for GABA can occur theoretically at either of two levels, at the level of its metabolism or at the level of its functioning. Convulsant agents such as picrotoxin and bicuculline appear to act by impairing the functioning of GABA at the postsynaptic receptor site, but virtually nothing is known about the attendant molecular events although a major expansion of knowledge in this area may be expected within the next decade. In contrast, a vast amount of data has accumulated with respect to changes in GABA metabolism induced by convulsant agents such as the hydrazines, hydrazides, and hyperbaric oxygen. The problem in this case lies in the interpretation of the data. Are the changes in GABA metabolism the cause of the seizures? There is clearly no simple relationship between seizure activity and any single parameter of GABA metabolism, be it the GABA content of the brain, or the rate of uptake of GABA by cellular components, or the activity of the GABA-synthesizing and degrading enzyme systems, GAD and GABA-T respectively. This finding may, however, be illusory since the parameters of GABA metabolism were in most cases measured using preparations from intact brain tissue. Observed changes in the parameters may not accurately reflect events at a critical subcellular location such as the synaptic cleft. Thus there may well be a simple relationship between the concentration of GABA in the synaptic cleft and seizure activity. Unfortunately the limitations of current technology preclude the testing of this possibility. The author has, however, developed an equation on an empirical basis which provides an excellent relationship between the excitable state of the brain and a function of GABA metabolism which incorporates both changes in GABA level and changes in GAD activity. This equation has been used successfully to explain and rationalize previously anomalous results with respect to changes in GABA metabolism associated with the action of both convulsant and anticonvulsant agents. The concept embodied in the equation is that the excitable state of brain is determined primarily by the rate of synthesis of GABA but that reflects changes in the concentration of GABA in the synaptic cleft has been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of gamma-aminobutyric acid in the mechanism of seizures. 83 81

Two clinically effective anticonvulsants, phenobarbitone and diazepam, protected 5-day old chicks against picrotoxin convulsions without reducing brain GABA-transaminase activity or raising brain GABA concentration. Ethanolamine-O-sulphate and amino-oxyacetic acid, in doses which inhibited GABA-transminase by at least 63% and approximately doubled brain GABA concentration, did not significantly affect the ED50 for picrotoxin convulsions. The ED50 for picrotoxin convulsions was significantly raised by di-n-propylacetate (800 mg/kg) which inhibited GABA transaminase activity by 6% and elevated brain GABA concentration by 26%.
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PMID:Picrotoxin convulsions and GABA metabolism after injection of anticonvulsants in chicks. 99 20

An electron cytochemical technique is described for the localization of GABA-T, the enzyme which degrades the neurotransmitter GABA, in rat cerebellar cortex. The technique allows ultrastructural demonstration of GABA-T activity by the final deposition of an electron dense formazan precipitate at reaction sites, whilst maintaining adequate ultrastructural preservation for recognition of cellular and subcellular structures. Numerous electron dense precipitates are evident as discrete punctate deposits situated mainly in mitochondria of stellate cells, basket cells and astrocytic glial cells; they are also seen in axonal or dendritic profiles at some synaptic junctions. The technique enables the first cytochemical demonstration of the mitochondrial localization of GABA-T activity in nervous tissue to be presented. It establishes that GABA-T is present in supposed GABA neurones, in pre- or post-synaptic endings, or both, of presumed inhibitory synapses and in glial cells which may be associated with these synapses. From this seemingly ubiquitous distribution, functional aspects of GABA-T in these cells is considered.
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PMID:Electron cytochemical localization of gamma-aminobutyric acid catabolism in rat cerebellar cortex. 99 62

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

Differences in the kinetic properties of brain gamma-aminobutyrate aminotransferase (GABA-transaminase; GABA-T) in different species are described in the present investigation. In both rat and human brain enzymes, the effect of temperature on the activity was studied. The maximal activity, for a 30-min incubation period, was attained at an incubation temperature of 45 degrees C for rat and 56 degrees C for human brain tissue. The addition of plasma or plasma proteins was found to induce a two-fold increase of the activity of rat brain GABA-T, whereas a slight inhibitory effect on human brain enzyme and no effect on mouse brain enzyme was observed. The species differences are shown to be the results of differences in the binding of the cofactor pyridoxal phosphate to the apoprotein, which are revealed when the free concentration of pyridoxal phosphate is reduced by binding to serum albumin.
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PMID:Studies on gamma-aminobutyrate aminotransferase (GABA-T) activities in human and rodent brain homogenates. 128 90

The in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.
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PMID:The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina. 130 60

The relationship between GABA dynamics and LH release was studied on day 2 after subcutaneous estrogen implant in short-term ovariectomized rats. GABA accumulation, used as an index of GABA turnover, was determined in the medial preoptic nucleus (MPN), medial (MS) and lateral (LS) septal nuclei, median eminence-mediobasal hypothalamus (MBH) and locus ceruleus (LC). Measurements of GABA were performed at two different times of day (11.00 and 15.00 h), 3 h after intraperitoneal administration of gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase. Either morning or afternoon ovariectomized rats (OVX) showed a significant increase in GABA accumulation after GVG treatment in all the areas studied. Estrogen-treated OVX rats showed in the morning a lower GABA accumulation in the MPN, MBH and LC, and GABA levels remained unchanged in the LS and MS. In the afternoon, the MPN and LS showed a lower rate of GABA accumulation whereas in the MBH and LC the GABA increase was not observed. In contrast the MS showed a rate of GABA accumulation similar as in the OVX rats. Local administration in the MPN of 20 micrograms GVG, or GABA-A receptor stimulation by muscimol (50 ng), prior to the increase in plasma LH levels, prevented the occurrence of the estradiol-induced LH surge. The effect of muscimol was reversed by bicuculline (30 ng), a GABA-A receptor antagonist. Bicuculline in low doses lacked effect by itself. In conclusion, these results strongly suggest that a decreased GABAergic activity in MPN, MBH and LC precedes the estradiol-evoked LH surges in ovariectomized rats. Moreover, that in septal nuclei, a low GABAergic activity takes place well before the occurrence of plasma LH increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Restraining action of GABA on estradiol-induced LH surge in the rat: GABA activity in brain nuclei and effects of GABA mimetics in the medial preoptic nucleus. 131 4

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


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