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)

4-Aminobutyrate transaminase (GABA-T, 4-aminobutyrate alpha-oxoglutrate aminotransferase, EC 2.6.1.19) is an enzyme that inactivates the inhibitory neurotransmitter, GABA, but its pharmacological function is uncertain. Two forms of guiena pig brain GABA-T were isolated by DEAE-cellulose chromatography and designated as GABA-T-I and II, corresponding to an anionic and a cationic form. The enzymes were inhibited by high concentrations of a cationic form. The enzymes were inhibited by high concentrations of alpha-oxoglutrate (alpha-KG). Kinetic consists for GABA, when determined at pH 7.9 adn 1 mmol/l alpha-KG, were 0.74 mmol/l. GABA-T activity was inhibited by chloride and other anions. Kinetic analysis revealed chloride ion as a conpetitive inhibitor against GABA, but the Ki values differed among GABA-T-I and II (Ki equals 120 and 60 mmol/l, respectively). Similar degrees of difference were observed with acetate and lactate ion. These results suggest that GABA-T-II may regulate the GABA level in the inhibitory neurons and may play a similar functional role as that exhibited by monoamine oxidase in other synapses.
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PMID:Two forms of 4-aminobutyrate transaminase in guinea pig brain. 23 77

Putrescine is the major source of gamma-aminobutyric acid (GABA) in the rat adrenal gland. Diamine oxidase, and not monoamine oxidase, is essential for GABA formation from putrescine in the adrenal gland. Aminoguanidine, a diamine oxidase inhibitor, decreases the GABA concentration in the adrenal gland by more than 70% after 4 h, and almost to zero in 24 h. Studies using [14C]putrescine confirm that [14C]GABA is the major metabolite of putrescine in the adrenal gland. Inhibition of GABA transaminase by amino-oxyacetic acid does not change the GABA concentration in the adrenal gland, as compared with the brain, where the GABA concentration rises. With aminoguanidine, the turnover time of GABA originating from putrescine in the adrenal gland is 5.6 h, reflecting a slower rate of GABA metabolism compared with the brain. Since GABA in the adrenal gland is almost exclusively derived from putrescine, the role of GABA may relate to the role of putrescine as a growth factor and regulator of cell metabolism.
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PMID:Putrescine, a source of gamma-aminobutyric acid in the adrenal gland of the rat. 313 1

Brain capillaries (microvessels) were isolated from the rabbit and bovine brain. Extensive morphological examinations were performed at the light and electron microscopical levels. The relative contribution of endothelium (52%), basal membrane (32%) and pericytes (16%) to the composition of the microvessel was assessed. The ability of the endothelium from bovine brains to maintain a membrane potential, i.e. to accumulate the lipophilic cation [3H]TPMP, was shown. The transmitter catabolizing enzymes MAO and AchE were shown to be, and COMT and GABA-T not to be associated with the microvessel fraction isolated from rabbits.
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PMID:On the composition and characteristics of microvessels isolated from the rabbit and bovine brain. 372 67

Brain capillaries (microvessels) were isolated from rabbit brain. Morphological characterization revealed relatively pure fractions of microvessels consisting of the capillary endothelium, the basal membrane, and the pericyte. These fractions of brain capillaries show acetylcholinesterase (AChE) and monoamine oxidase (MAO) activity, but lack catechol-O-methyltransferase and GABA transaminase activity. Isolated brain capillaries together with samples of the brain parenchyma and serum were used to study the role of AChE present in the brain capillary wall in soman intoxication. The results showed this AChE to be less sensitive to soman inhibition than AChE of brain parenchyma. Serum and brain AChE recovered to some extent in soman-intoxicated rabbits given HI-6, whereas AChE present in the microvessel was even further inhibited. It is suggested that soman-induced vasospasm in rabbit brain may explain both the inaccessibility of capillary AChE to soman and also the unfavorable effect of HI-6 on this enzyme.
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PMID:Soman intoxication and the blood-brain barrier. 409 83

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

Lipid peroxide levels, were found to be significantly higher in brains of 18 month old as compared to 4 month old rats, with particularly large increases occurring in the olfactory bulb, globus pallidus, cerebral cortex and caudate-putamen (CP). Eighteen month old rats fed a vitamin E deficient diet for 9 months before sacrifice had lipid peroxide levels significantly higher than age-matched controls in the cerebral cortex, hippocampus and hypothalamus. Age-related decreases were seen in choline acetyltransferase, acetylcholinesterase and 3H-QNB binding in some but not all brain regions, while GABA transaminase and MAO showed age-related increases. No age-related change was seen in tyrosine hydroxylase in the CP or in 3H-dihydroalprenolol (DHA) or 3H-spiroperidol binding in the cortex. As compared with controls, vitamin E deficient rats showed decreases of 38% in cortical 3H-DHA binding, of 33% in 3H-QNB binding in the CP and of 23% and 12% in choline acetyltransferase in the CP and cerebellum, respectively. There were no completely consistent regional correlations between significant changes in lipid peroxidase levels and any neurotransmitter indices studied except for MAO which was only measured in the caudate-putamen.
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PMID:Lipid peroxides in brain during aging and vitamin E deficiency: possible relations to changes in neurotransmitter indices. 613 87

The activities of monoamine oxidase (MAO), catechol-O-methyltransferase (COMT) and gamma-aminobutyric acid transaminase (GABA-T) were measured in primary cultures from newborn rat cultivated from 6 different brain regions. These primary cultures contained mostly astroglial cells, evaluated by the presence of the glial fibrillary acidic protein (GFAp, alpha-albumin) and the S-100 protein. The enzyme activities in the corresponding brain area from adult rat were also quantified. MAO activities were on the same level in 14-day old cultures and in adult rat brain homogenates, with significantly lower values in brain stem as compared to the other brain regions examined. COMT activities were on a higher level in the cultures than in adult rat brain homogenates. Astroglial cells from hippocampus were found to have the highest and those from brain stem the lowest COMT-activities. GABA-T activities were lower in the cultures than in adult rat homogenates. No significant differences were seen in the various astroglial cultures. Accumulation of [3H]dopamine and [3H]gamma-aminobutyric acid (GABA) visualized by autoradiography showed only a slight uptake of dopamine in comparison with the uptake of GABA. It is concluded that astroglial cells in culture have enzymatic properties similar to those of astroglial cells in different brain regions of adult rat brain. Studies are in progress to evaluate if the regional heterogeneity observed among cultivated astroglial cells is affected by in vivo differentiation until cultivation and/or time in culture.
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PMID:Enzyme activities of monoamine oxidase, catechol-O-methyltransferase and gamma-aminobutyric acid transaminase in primary astroglial cultures and adult rat brain from different brain regions. 671 30

The crude mitochondrial fraction of rat brain contains an active dehydrogenase involved in the direct oxidation of gamma-aminobutyric acid. INT (p-iodonitrotetrazolium violet) can serve as an efficient acceptor of electrons in this dehydrogenase reaction. During this oxidation of GABA, ammonia is not produced. In vitro the dehydrogenase activity is inhibited by certain MAO inhibitors. The effects of various inhibitors of GABA-T and GAD were also investigated. The dehydrogenase activity was found to be susceptible to various anti-convulsants and inhibitors of electron transport. The co-factors which may be involved in the transfer of electrons during GABA oxidation in the presence of INT are also discussed.
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PMID:GABA dehydrogenase activity in rat brain. 715 Mar 50

The MAO inhibitor phenelzine (2-phenylethylhydrazine; PLZ) is used widely in psychiatry for the treatment of depression and panic disorder. Its N-acetyl metabolite, N2-acetylphenelzine (N2AcPLZ) is a reasonably potent nonselective inhibitor of monoamine oxidase (MAO) that causes elevation in brain levels of the biogenic amines. In the studies reported here, PLZ (0.05 mmol/kg/day), N2AcPLZ (0.10 mmol/kg/day) or vehicle were administered to male rats for 28 days s.c. with Alzet minipumps, and their effects on GABAergic function were examined. Whole brain concentrations of gamma-aminobutyric acid (GABA) were significantly elevated in the PLZ but not in the N2AcPLZ-treated group. PLZ was found to inhibit the anabolic enzyme glutamic acid decarboxylase (GAD) and, to a greater extent, the catabolic enzyme GABA transaminase (GABA-T). The results of these investigations suggest that the free hydrazine moiety in PLZ is crucial to producing the elevated levels of GABA, probably through inhibition of GABA-T. Despite the considerable increase in whole brain GABA levels in the PLZ-treated rats, there were no significant differences in GABAA or benzodiazepine receptor binding parameters (KD or Bmax) between the groups as measured using 3H-muscimol and 3H-flunitrazepam in radioligand binding assays.
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PMID:Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function. 793 Dec 16

The antidepressant/antipanic drug phenelzine (PLZ) is both an inhibitor of, and a substrate for, monoamine oxidase (MAO). PLZ also causes an elevation of brain levels of the amino acid neurotransmitter gamma-aminobutyric acid (GABA); this action can be reversed by pretreatment with the MAO inhibitor tranylcypromine (TCP), suggesting that the GABA-elevating effect is largely the result of a metabolite of PLZ formed by MAO. In the present report, rats were pretreated with the nonselective MAO inhibitor TCP, the MAO-A inhibitor clorgyline and the MAO-B inhibitor (-)-deprenyl: at the doses used, clorgyline and (-)-deprenyl caused selective inhibition of MAO-A and MAO-B, respectively. Both TCP and (-)-deprenyl caused a greater reduction in the GABA-elevating action of PLZ than did clorgyline, suggesting that MAO-B is more important than MAO-A in the formation of the active metabolite of PLZ. The results also suggest that an effect other than, or in addition to, inhibition of GABA transaminase by the metabolite may be important in the GABA-elevating action.
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PMID:GABA-elevating effects of the antidepressant/antipanic drug phenelzine in brain: effects of pretreatment with tranylcypromine, (-)-deprenyl and clorgyline. 874 40


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