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 raphe nuclei [which contain serotonin (5-HT) cell bodies] are also known to contain axons that store substance P, met-enkephalin, and gamma-aminobutyric acid (GABA). We have previously shown that GABA has a tonic inhibitory action on 5-HT turnover. To examine other possible interactions of these neuronal systems, we assessed the effect on 5-HT turnover of injecting substance P and 2-D-ala-met-enkephalin into the median raphe nucleus, and the effects of substance P on GABA turnover. Serotonin turnover was increased by 30% in the hippocampus after the injection of substance P (4 micrograms) into the median raphe, indicating an excitatory effect of substance P on the raphe-hippocampal system. Local injection of the metabolically stable metenkephalin analog 2-D-ala-met-enkephalin amide (10 micrograms) increased the hippocampal steady state content of 5-hydroxyindoleacetic acid (5-HIAA) by 60%. The data suggest an excitatory effect of met-enkephalin within the raphe nucleus. We attempted to estimate GABA turnover from the rate of disappearance of GABA after inhibition of glutamic acid decarboxylase by isoniazid and by the rate of accumulation of GABA after inhibition of GABA transaminase by gabaculine. Isoniazid, which is a competitive inhibitor, had too short and incomplete an action to be of use when injected intranuclearly. Gabaculine, which is an irreversible inhibitor, induced a rapid-onset increase in GABA content. This accumulation was linear up to 90 min. The injection fo gabaculine (80 ng) into the raphe increased GABA content by five times the control values, but hippocampal 5-HT and 5-HIAA contents were not significantly changed. Substance P injection increased the GABA turnover by 30%. Gabaculine seems a promising tool for detecting changes in GABA turnover.
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PMID:Serotonin and gamma-aminobutyric acid turnover after injection into the median raphe of substance P and D-ala-met-enkephalin amide. 617 97

Histochemical and biochemical studies demonstrate that gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (EC 4.1.1.15), and GABA aminotransferase (EC 2.6.1.19) are present in bovine adrenal chromaffin cells. Moreover, [3H]GABA can be taken up and stored by primary cultures of adrenal chromaffin cells. Nicotinic receptor stimulation or KCl depolarization releases the [3H]GABA taken up by these cell cultures. GABA and benzodiazepine recognition sites located in chromaffin cells interact with each other with modalities similar to those described for GABA and benzodiazepine recognition sites located in synaptic membranes prepared from brain tissue. Bicuculline facilitates the release of catecholamine from chromaffin cells induced by nicotinic receptor stimulation but it fails to influence the release of catecholamine evoked by K+ depolarization. Since the GABA-benzodiazepine receptor system appears to modulate nicotinic receptor function, it is suggested that GABA transmission might participate in modulating responsiveness of chromaffin cells to incoming cholinergic stimuli.
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PMID:Intrinsic GABAergic system of adrenal chromaffin cells. 632 6

The effects of the glutamic acid decarboxylase inhibitor 3-mercaptopropionic acid (MPA) on the concentration of GABA in the mouse brain were studied. MPA completely inhibited the postmortem increase in GABA. This effect was used in order to achieve a maximal inhibition of the GABA synthesis in vivo during 67.5 minutes before killing by giving the drug repeatedly (50 mg/kg + 6 X 10 mg/kg i.p.) to mice pretreated with chloral hydrate (100 mg/kg i.p., 65 min before killing). Such a treatment with MPA markedly reduced the accumulation of GABA following inhibition of the GABA transaminase by aminooxyacetic acid but it did not change the endogenous concentration of GABA. This discrepancy might be due to inhibition of the impulse--evoked release of GABA following MPA.
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PMID:Effects of the glutamic acid decarboxylase inhibitor 3-mercaptopropionic acid on the synthesis of brain GABA in vivo and postmortally. 665 69

The effects of drugs that antagonize or potentiate the action of brain gamma-aminobutyric acid (GABA) on shock-induced aggressive behavior in mice were investigated. In previous studies it has been shown that in C57 BL/6 strain shock-induced aggressive behavior is absent up to the 10th week of age and rises to the highest intensity after the 20th week, while at the same ages aggressive responses are lowest or absent in DBA/2 strain. GABA antagonist, picrotoxin and glutamic acid decarboxylase (GAD) inhibitor, D, L-allylglycine induced aggressive responses in non-aggressive 10 week old C57 BL/6 and 20 week old DBA/2 mice. GABA agonist muscimol hydrobromide, and GABA-T inhibitor sodium n-dipropylacetate inhibited aggressive responses in 20 week old C57 BL/6 mice. These effects were not related to changes in shock sensitivity and motor activity. The results strongly suggest that the GABAergic system is involved in the control of shock-induced aggressive behavior in mice and that this control is related to developmental and genetic factors.
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PMID:Involvement of the GABAergic system on shock-induced aggressive behavior in two strains of mice. 678 19

The slow onset and carry-over effect of valproic acid (VPA) therapy observed in some clinical as well as experimental animal studies have been examined by parallel pharmacokinetic and pharmacological investigations in a mouse model. VPA was rapidly transferred into brain and was cleared from that tissue with rates which exceeded plasma clearance rates. Of several VPA metabolites present in plasma, only one could be found in the brain: 2-propyl-2-pentenoic acid. This metabolite was cleared from plasma and from brain slower than the parent drug. gamma-Aminobutyric acid (GABA) concentrations were increased within 15 min after VPA injection and remained significantly elevated for at least 8 h. A similar time course was found in regard to the increase of the electroconvulsive threshold (maximal seizures) induced by VPA administration. The activity of glutamic acid decarboxylase rose parallel to the elevation of brain GABA levels, whereas the activity of GABA aminotransferase was not affected. Whereas the rapid onset of the effect on electroconvulsive threshold and on GABA metabolism can be explained by the rapid entrance of VPA into brain, the carry-over effects observed correlated with the kinetics of the metabolite 2-propyl-2-pentenoic acid better than with those of VPA due to the persistence of this metabolite in brain.
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PMID:Valproic acid: brain and plasma levels of the drug and its metabolites, anticonvulsant effects and gamma-aminobutyric acid (GABA) metabolism in the mouse. 680 Dec 54

Mice were treated with different doses of the GABA aminotransferase (GABA-T) inhibitors aminooxyacetic acid, gamma-acetylenic acid, gamma-vinyl GABA and ethanolamine-O-sulphate via the drinking water for periods of 1-12. All drugs caused marked elevations of whole brain GABA concentrations within 4 days of treatment which were associated with increases in the electroconvulsive threshold. However, the effect on seizure threshold could not be enhanced by an increase in the daily dosage of the GABA-T inhibitors and, especially with higher doses, tolerance to the anticonvulsant effect developed. At least in part, this finding may be attributed to a decrease in the activity of glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis. On the other hand, with valproic acid (VPA) no tendency towards a reduced anticonvulsant effectiveness during medication was observed. VPA caused only non-significant increases in cerebral GABA levels but elevated brain GAD activity significantly. No behavioral changes were seen following subchronic administration of GABA-T inhibitors and VPA except in cases where the daily fluid intake was markedly reduced. Our data suggest that the anticonvulsant efficacy of long term treatment with GABA-T inhibitors is limited by the development of compensatory mechanisms, such as reduction of GAD activity, which in turn reduce the amount of GABA available for synaptic transmission, though overall GABA concentrations in the brain are highly elevated. Drug such as VPA which cause only moderate effects on GABA metabolism seem superior in this respect.
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PMID:Anticonvulsant and biochemical effects of inhibitors of GABA aminotransferase and valproic acid during subchronic treatment in mice. 680 73

Mice were continuously treated with valproic acid (VPA) via the drinking water for period from 1 to 12 days. The daily drug intake varied between 500 and 580 mg/kg. However, due to the rapid elimination of VPA in this species average plasma concentrations of only 3-4 micrograms/ml VPA were present at 8:30 a.m., the time chosen for determinations. In the brain, VPA levels were about 10% of those in plasma. In regard to VPA metabolism the products of beta-oxidation 2-en-VPA 2-propyl-2-pentenoic acid) and 3-keto-VPA (2-propyl-3-oxopentanoic acid) proved to be the main metabolites in plasma although other (minor) metabolites of VPA were also present. The only metabolite of VPA detected in the brain was 2-en-VPA. VPA medication caused a significant increase in the threshold for electroconvulsions which was associated with a slight increment of brain GABA levels. The activity of glutamic acid decarboxylase was significantly elevated whereas GABA aminotransferase was not affected. After withdrawal of VPA, a delayed effect on seizure threshold was observed which extended to time periods where VPA could no longer be detected in the brain, but 2-en-VPA was still present.
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PMID:Valproic acid: metabolite concentrations in plasma and brain, anticonvulsant activity, and effects on GABA metabolism during subacute treatment in mice. 681 Jul 78

Regional distribution of endogenous gamma-aminobutyric acid (GABA), its synthesizing enzyme, glutamic acid decarboxylase (GAD), and metabolic enzyme, GABA transaminase (GABA-T), were determined in the intestinal tract of guinea pigs and cats and the findings compared with the number of ganglion cells in Auerbach's plexus. There were positive correlations among the GABA contents and the numbers of neural cells of the plexus. The precise localization of GABA and GAD in individual layers (mucosa, circular and longitudinal muscles, and Auerbach's plexus) in the human and cat colon was also determined. The endogenous GABA contents and GAD activity were the highest in Auerbach's plexus in tissues of both species. These results indicate that GABA is synthesized and localized in Auerbach's plexus and probably plays a significant role in the enteric nervous system.
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PMID:GABA, glutamic acid decarboxylase, and GABA transaminase levels in the myenteric plexus in the intestine of humans and other mammals. 682 80

The effects of local anesthetics on the synthesis, release, and degradation of gamma-aminobutyric acid (GABA) in rat brains were investigated. The addition of procaine, lidocaine, cocaine, or tetracaine did not alter either glutamic acid decarboxylase (GAD) activity or GABA transaminase (GABA-T) activity in vitro. Neither did the enzyme activities in rats with local anesthetic-induced convulsions differ from control values. Tetracaine inhibited high K+-evoked [2,3-3H]GABA release from synaptosomes of rat brain in a dose-dependent manner with a minimal effective concentration of 10(-4) M. Cocaine, lidocaine, and procaine also reduced the release, although they were less potent than tetracaine. The GABA release inhibitors in order of potency are tetracaine, cocaine, lidocaine, and procaine which correlates well with their relative toxicity as convulsants. These results suggest that local anesthetics reduce GABAergic activities by inhibiting the release of the neurotransmitter from the nerve terminals, and that inhibition of the GABA system may be involved in the mechanism of local anesthetic-induced convulsions.
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PMID:Inhibition of gamma-aminobutyric acid release from synaptosomes by local anesthetics. 685 79

The effects of gamma-aminobutyric acid (GABA)-alpha-oxoglutarate aminotransferase (GABA-T) inhibitors, L-glutamic acid decarboxylase (GAD) inhibitors, and antipetit mal anticonvulsants on gamma-hydroxybutyric acid (GHB) and GABA were studied. Treatment with anticonvulsants and GABA-T inhibitors resulted in an increase in steady-state brain levels of both GHB and GABA. GAD inhibitors produced markedly decreased levels of brain GABA but no change in GHB concentrations. Studies of GHB derived exclusively from GABA showed that GABA-T inhibitors which produced an elevation of steady-state levels of GHB in brain also resulted in a decrease in GABA-derived GHB. Intracerebroventricular (i.c.v.) administration of GABA, putrescine, and 1,4-butanediol all produced significant elevations in brain GHB, but GABA-T inhibitors blocked this effect of GABA and putrescine. These data suggest that there may be another source for GHB in brain in addition to GABA and raise the possibility that 1,4-butanediol may be that source.
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PMID:Studies on the relation of gamma-hydroxybutyric acid (GHB) to gamma-aminobutyric acid (GABA). Evidence that GABA is not the sole source for GHB in rat brain. 715 69


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