Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.19 (GABA transaminase)
 808 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several benzodiazepines (chlordiazepoxide, clonazepam, diazepam and flunitrazepam) markedly counteracted the elevation of the homovanillic acid (HVA) content of the rat brain induced by neuroleptics (haloperidol, pimozide, chlorpromazine, and clozapine). A similar effect was obtained with the inhibitor of GABA transaminase, aminooxyacetic acid (AOAA). The interaction of benzodiazepines with the neuroleptic-induced HVA increase was similar in the striatum and in the limbic forebrain and was antagonized by the GABA receptor-blocking agent, picrotoxin. Both the benzodiazepines used and AOAA potentiated the cataleptic effect of the four neuroleptics. It is concluded that benzodiazepines, by intensifying GABA-ergic transmission, enhance the ongoing inhibition of mesencephalic dopamine neurons exerted by the striatonigral GABA system. As a consequence, the feedback activation of dopamine neurons induced by the neuroleptic blockade of dopamine receptors in the striatum and the limbic system is attenuated. This results in a reduction of the neuroleptic-induced increase of HVA and in the potentiation of the cataleptic effect of neuroleptics.
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PMID:Interaction of benzodiazepines with neuroleptics at central dopamine neurons. 1 77

Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.
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PMID:Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines. 3 40

In the neostriatum of adult rats the distribution of Dopamine and GABA was investigated by means of fluorescence histochemical methods. There is a different mode of distribution of the transmitters in this brain region. The animals were treated with cycloserin, acting as an inhibitor of the GABA transaminase, in order to enhance the GABA content. In the neostriatum GABA containing neurons and GABA-ergic afferents could be demonstrated. GABA containing fibers are present in the whole striatum. Varicose Dopamine fibers appear as a dense fluorescent network.
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PMID:[Fluorescence histochemical investigations on the topic of GABA and dopamine in the neostriatum of the rat (author's transl)]. 11 31

Glutamate decarboxylase, gamma-aminobutyrate-alpha-ketoglutarate aminotransferase and NAD-linked and NADP-linked succinic semialdehyde dehydrogenase, all constituting the GABA (gamma-aminobutyrate)-shunt pathway of glutamate metabolism are localized in the mitochondrial matrix in a streptomycin-bleached mutant of Euglena gracilis strain Z. Glutamate dehydrogenase, requiring NADP as the cofactor, was distributed in the cytoplasm. An improved version of the controlled digestion method for preparing Euglena mitochondria, which involves use of trypsin and a trypsin inhibitor and removal of broken cells before mechanical disruption of cells, is also described.
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PMID:Subcellular localization of the GABA-shunt enzymes in Euglena gracilis strain Z. 11 50

Regional brain GABA distribution studies show that after administration of sodium n dipropylacetate, a competitive inhibitor of GABA transaminase, the concentration of GABA increases in some regions i.e. Olfactory Bulbs, Hypothalamus, Cortex, Cerebellum. The GABA level remains unchanged in Caudate Nucleus, Pons Medulla, Hippocampus in our experimental conditions. These variations do not correlate with the initial GABA level.
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PMID:[Effects of sodium n-dipropylacetate on the GABA level in various areas of the mouse brain]. 14 Jul 50

We describe clinical and biochemical changes in seven patients with Huntington disease given isoniazid (INH) in dosages three to five greater than normally used in tuberculosis. Because INH inhibits the enzyme gamma-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease. Of six patients treated long enough to be clinically evaluated, one showed marked and two others showed signifciant improvement. High-dose INH therapy carries serious toxic risks, which are influenced by patients' acetylator phenotypes. Nevertheless, results are sufficiently promising to warrant further controlled trials of INH or other GABA-T inhibitors in Huntington disease.
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PMID:Isoniazid therapy of Huntington disease. 15 13

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of mammalian brain GABA transaminase that produce several-fold increases in brain GABA concentrations were tested for their effects on bicuculline and picrotoxin-induced seizures and mortality in mice. Neither inhibitor influenced the frequency of seizures or death produced by either bicuculline or picrotoxin. Both inhibitors, however, produced a dose-dependent prolongation of the time to onset of seizures and death induced by picrotoxin but by bicuculline. These results suggest differences in the antagonism by bicuculline and picrotoxin of GABA-mediated neural functions.
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PMID:Effect of elevated brain GABA concentrations on the actions of bicuculline and picrotoxin in mice. 20 Sep 66

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

A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. We conclude that either the sodium valproate inhibition of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures.
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PMID:Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. 35 31

A detailed presentation of 15 case-histories of subjects of both sexes, drawn from all decennies of life from the first to the eight, suggesting a syndrome originated from a possible GABA deficiency, is carefully made. Such syndrome is believed to be characterized by basic depressive state, loss of the habit of stretching oneself, sleep disorders, mostly with early morning awakening, constipation and nuchal headache. The above symptoms have been associated to a deficiency of GABA after noting the very speed recovery after administration of N-dipropylacetic acid, an inhibitor of GABA transaminase.
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PMID:A syndrome from a possible GABA deficiency. Clinical-therapeutic report on 15 cases. 35 28


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