UNIPROT:P80404 - FACTA Search

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Query: UNIPROT:P80404 (GABA transaminase)
786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects were examined of two inhibitors of GABA-aminotransferase, amino-oxyacetic acid (AOAA) and RMI-71645-16, on depolarization-induced (30 mM K+) dopamine (DA) release from rat striatal slices. When added to the medium, these drugs increased the release of radiolabeled DA, either accumulated by high-affinity uptake or synthesized from 14C-tyrosine. AOAA did not modify the release of 14C-acetylcholine from striatal slices or 3H-noradrenaline from cortical slices. Moreover, 3H-DA release from substantia nigra was not affected. The data suggest the possibility that the effects of GABA-T inhibitors on striatal DA release are mediated by intrinsic GABA-ergic neurons.
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PMID:Increased dopamine release from rat striatal slices by inhibitors of GABA-aminotransferase. 59 Mar 29

The uptake and release of 3H-dopamine was studied in slices of corpus striatum and substantia nigra in the presence of nialamide. High potassium triggered the outflow of tritium in both brain structures and this release was potentiated by GABA in a dose related fashion, whereas the spontaneous overflow of radioactivity was unchanged. This action of GABA was mimicked by the GABA-T antagonists aminooxyacetic acid and ethanolamine-O-sulphate, but not by the GABA analogues muscimol, 3-aminopropanesulphonic acid, gamma-hydroxybutyrate or beta-(p-chlorophenyl)-GABA. The response to GABA was not blocked by picotoxin, which itself facilitated the evoked release of 3H-dopamine, nor by bicuculline or the omission of calcium ions from the bathing medium. GABA facilitation of K+-evoked 3H-dopamine release was increased significantly on reducing tissue thickness and following prolonged incubation with GABA. GABA also potentiated the depolarization induced outflow of 3H-noradrenaline, 3H-5-hydroxytryptamine and 3H-histamine without affecting their initial accumulation. Veratridine, amphetamine and cold dopamine also raised the output of 3H-dopamine, but none of these releases was altered by GABA. The uptake of 3H-dopamine, but not that of 14C-GABA, was considerably attenuated in 6-hydroxydopamine lesioned corpora striata. The possible mechanism(s) of this stimulatory action of GABA is discussed.
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PMID:GABA-mediated potentiation of amine release from nigrostriatal dopamine neurones in vitro. 75

1. 3H-gamma-Aminobutyric acid (GABA) release elicited by a depolarizing K+ stimulus or by noradrenergic transmitter was examined in rat pineals in vitro. 2. The release of 3H-GABA was detectable at a 20 mM K+ concentration in medium and increased steadily up to 80 mM K+. 3. In a Ca2+-free medium 3H-GABA release elicited by 30 mM K+, but not that elicited by 50 mM K+, became blunted. 4. Norepinephrine (NE; 10(-6)-10(-4) M) stimulated 3H-GABA release from rat pineal explants in a dose-dependent manner. 5. The activity of 10(-5) M NE on pineal GABA release was suppressed by equimolecular amounts of prazosin or phentolamine (alpha 1- and alpha 1/alpha 2-adrenoceptor blockers, respectively) and was unaffected by propranolol (beta-adrenoceptor blocker). 6. The alpha 1-adrenoceptor agonist phenylephrine (10(-7)-10(-5) M) and the beta-adrenoceptor agonist isoproterenol (10(-5) M) mimicked the GABA releasing activity of NE, while 10(-7) M isoproterenol failed to affect it; the alpha 2-adrenoceptor agonist clonidine (10(-7)-10(-5) M) did not modify 3H-GABA release. 7. The addition of 10(-4) M GABA or of the GABA transaminase inhibitor gamma-acetylenic GABA or aminooxyacetic acid inhibited the melatonin content and/or release to the medium in rat pineal organotypic cultures. 8. GABA at concentrations of 10(-5) M or greater partially inhibited the NE-induced increase in melatonin production by pineal explants. 9. The depressant effect of GABA on melatonin production was inhibited by the GABA type A receptor antagonist bicuculline; bicuculline alone increased the pineal melatonin content. Baclofen, a GABA type B receptor agonist, did not affect the pineal melatonin content or release. 10. The decrease in serotonin (5-HT) content of rat pineal explants brought about by NE was not modified by GABA; GABA by itself increased 5-HT levels. 11. These results indicate that (a) GABA is released from rat pineals by a depolarizing stimulus of K+ through a mechanism which is partially Ca2+ dependent; (b) NE releases rat pineal GABA via interaction with alpha 1-adrenoceptors; (c) GABA inhibits melatonin production in vitro via interaction with GABA type A receptor sites; and (d) GABA's effect on NE-induced melatonin release does not correlate with the lack of effect on the NE-induced decrease in pineal 5-HT content.
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PMID:Release and effect of gamma-aminobutyric acid (GABA) on rat pineal melatonin production in vitro. 247 90

The purpose of this paper was to study the relationship between different neurotransmitter systems and seizure susceptibility in Mongolian gerbils with genetically determined epilepsy. In these animals, generalized tonic-clonic seizures were induced by stimulation with a blast of compressed air. A variety of drugs that specifically manipulate inhibitory or excitatory neurotransmitter systems proved capable of dose dependently blocking these seizures, i.e., the anticholinergic drug biperiden (ED50 12 mg/kg i.p.), the excitatory amino acid antagonist (+/-)-2-amino-7-phosphonoheptanoic acid (120 mg/kg), the gamma-aminobutyric acid (GABA) agonists muscimol (0.66 mg/kg), 4,5,6,7-tetrahydroisoxazolo(5,4-c) pyridine-3-ol (1.3 mg/kg), progabide (50 mg/kg) and its acidic metabolite SL 75102 (45 mg/kg), the GABA aminotransferase inhibitors aminooxyacetic acid (0.9 mg/kg), gamma-acetylenic GABA (2.1 mg/kg) and ethanolamine-O-sulfate (1000 mg/kg), the GABA uptake inhibitor (-)-nipecotic acid ethyl ester (21 mg/kg), the dopamine agonist apomorphine (approximately 5 mg/kg), the dopamine precursor 3,4-dihydroxy-L-phenylalanine (34 mg/kg), and the alpha-adrenoceptor agonists clonidine (0.38 mg/kg) and xylazine (approximately 10 mg/kg). The anticonvulsant effect of 3,4-dihydroxyl-L-phenylalanine was not significantly affected by pretreatment with the dopamine-beta-hydroxylase inhibitors disulfiram and diethyldithiocarbamate, thus strongly indicating that 3,4-dihydroxyl-L-phenylalanine was acting through increase in dopamine rather than noradrenaline levels in the brain. The (+)-isomer of nipecotic acid ethyl ester, the glycineamide derivative milacemide, the indirect 5-hydroxytryptamine agonist fenfluramine and the 5-hydroxytryptamine antagonist ketanserin exerted no anticonvulsant action. The 5-hydroxytryptamine precursor L-5-hydroxytryptophan and the dopamine agonist lisuride were only weakly active but exerted pronounced side effects in the animals. Weak anticonvulsant effects were also determined for atropine, the noradrenaline precursor DL-threo-3,4-dihydroxyphenylserine and the excitatory amino acid antagonist (+/-)-2-amino-5-phosphonopentanoic acid. Comparison of anticonvulsant potencies of the various drugs in gerbils with potencies reported in other genetic animal models of epilepsy, such as audiogenic seizure-susceptible mice, indicated that drugs that increase GABA and dopamine levels in the brain are strikingly more effective in gerbils than in other species in blocking generalized seizures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of pharmacological manipulation of inhibitory and excitatory neurotransmitter systems on seizure behavior in the Mongolian gerbil. 285 79

Previous studies have suggested that gamma-aminobutyric acid (GABA) exerts inhibitory actions on luteinizing hormone (LH) secretion that are likely to be mediated by modifications in noradrenergic transmission. To explore further this hypothesis we have studied the effect of increasing GABA contents in discrete areas of the brain on plasma LH levels in short-term orchidectomized rats. GABA accumulation was produced by the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG). The locus coeruleus area (LC), where the noradrenaline (NA) cells projecting through the dorsal noradrenergic bundle are located, and several hypothalamic areas that are innervated by NA-containing fibers were microinjected with GVG. Most of these areas are known to be related to the neural control of LH secretion. GVG microinjected in the LC and medial preoptic area increased the GABA content and blunted significantly the acute increase of plasma LH produced by castration. Bicuculline prevented these effects. Delayed effects of GVG were observed when applied in the anterior hypothalamic area and ventromedial-arcuate nucleus area. In these latter areas, a single injection of GVG did not augment the GABA concentrations and was unable to prevent LH release, but a clear inhibitory effect took place after a second injection of GVG between 24 and 48 h after orchidectomy. Unresponsive areas to GVG treatment were the lateral preoptic area, the median eminence and the dorsal raphe. These results add support to the view that GABA inhibits LH release in rats, at discrete areas of the brain.
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PMID:Localized increase of GABA levels in brain areas of the rat and inhibition of the plasma LH rise following orchidectomy. 322 82

1. Oral administration of the GABA transaminase inhibitor ethanolamine-O-sulphate (EOS, 5 mg/ml in drinking water) to rats for 14 days suppressed food intake by 24%, but reduced weight gain by over 35%. 2. Thus, feed efficiency (g gain/MJ eaten) was decreased by over 15% in EOS-treated rats, suggesting that there had been an increase in metabolic rate. 3. The thermogenic response (rise in oxygen consumption, VO2) to injection of noradrenaline was enhanced by 50% and the thermogenic activity of brown adipose tissue (BAT, assessed from mitochondrial GDP-binding) was increased by 38% in EOS-treated rats. 4. Injection of baclofen (a GABAB agonist, 0.5 mg/kg s.c.) stimulated VO2 in both groups, with a significantly greater response in EOS treated rats, and this was enhanced by bicuculline (GABAA antagonist, 0.5 g/kg s.c.) in control rats and attenuated by muscimol (GABAA agonist, 0.5 mg/kg s.c.) in control and EOS-treated rats. 5. The data indicate that increasing brain GABA concentrations with EOS results in lower levels of metabolic efficiency and increases in thermogenesis.
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PMID:Chronic inhibition of GABA transaminase results in activation of thermogenesis and brown fat in the rat. 341 1

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

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

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium iodide (MPP+) and gamma-vinyl-gamma-aminobutyric acid (gamma-vinyl GABA) are drugs demonstrated to alter catecholamine or gamma-aminobutyric acid (GABA) concentrations in vertebrate nervous tissue. MPTP and MPP+, which are potent and selective vertebrate neurotoxins, are effective in depleting noradrenaline and dopamine concentrations in goldfish. However, only MPP+ depletes dopamine in the central nervous tissues of the cockroach, and only when injected directly into the nervous tissue. Systemic injection of gamma-vinyl GABA, a selective GABA transaminase inhibitor in vertebrates, increases GABA concentrations in goldfish but not cockroach nervous tissue. Incubations of both goldfish hypothalamus and cockroach nervous tissue demonstrated the presence of GABA transaminase activity in vitro. However, the GABA transaminase activity obtained from goldfish tissues was much more sensitive to inhibition by gamma-vinyl GABA than that obtained from cockroach nervous tissue. These results demonstrate that MPTP, MPP+ and gamma-vinyl GABA are useful pharmacological tools which can alter neurotransmitter concentrations in a lower vertebrate. Unfortunately, they possess limited effectiveness in the cockroach.
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PMID:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and gamma-vinyl-gamma-aminobutyric acid (gamma-vinyl GABA) alter neurotransmitter concentrations in the nervous tissue of the goldfish (Carassius auratus) but not the cockroach (Periplaneta americana). 809 92

1. The modulatory effects of L-glutamate and its structural analogues, and of gamma-aminobutyric acid (GABA), on sympathetic co-transmission were studied in the rat isolated vas deferens exposed to electrical field stimulation (EFS). 2. Application of exogenous L-glutamate caused a concentration-dependent (1 microM-3 mM) inhibition of the rapid twitch component of the biphasic EFS contraction. However, L-glutamate (1 microM-3 mM) had a minimal effect on the phasic contraction induced by exogenous adenosine 5'-triphosphate (ATP, 150 microM) and noradrenaline (50 microM). Unlike L-glutamate, D-glutamate had no effect on the EFS contraction. 3. The L-glutamate-induced inhibition of the EFS contractions was significantly attenuated by the glutamate decarboxylase (GAD) inhibitor 3-mercapto-propionic acid (150 microM) and was abolished in the presence of the GABA transaminase (GABA-T) inhibitor, 2-aminoethyl hydrogen sulphate (500 microM). 4. The L-glutamate-induced inhibition of the electrically evoked contraction was not affected by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)(30 nM), reactive blue 2 (30 microM) or the GABAA receptor antagonist bicuculline (50 microM). However, the GABAB receptor antagonist 2-hydroxysaclofen (50 microM) significantly inhibited the L-glutamate effect. 5. Similar to L-glutamate, GABA also caused a concentration-dependent (0.1-100 microM) inhibition of the EFS contractions. This GABA-induced inhibition was not affected by either the GABAA receptor antagonist bicuculline (50 microM) or reactive blue 2 (30 microM). However, a significant attenuation of the GABA-mediated effect was recorded with the GABAB receptor antagonist 2-hydroxysaclofen (50 microM). Contractions of the vas deferens induced by exogenous ATP and noradrenaline were not affected by GABA (0.1-100 microM). 6. The L-glutamate analogues, N-methyl-D-aspartate (NMDA) (1 microM-1 mM) and quisqualate (Quis 0.1 microM-0.3 mM) had no effect, whilst kainate (Kain, 1 microM-1 mM) caused an inhibition of the EFS-induced contractions. Effects of Kain could be abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dioxine (CNQX, 10 microM). NMDA, Quis and Kain had no effect on the exogenous ATP- or noradrenaline-induced contractions. 7. It is concluded that the excitatory amino acid L-glutamate modulates the electrically evoked vas deferens contraction through conversion to the inhibitory amino acid GABA by a specific GABA transaminase. The GABA formed may then act on GABAB receptors and cause inhibition of the contraction through a presynaptic mechanism.
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PMID:Presynaptic modulation by L-glutamate and GABA of sympathetic co-transmission in rat isolated vas deferens. 876 4

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