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)

Characteristics of 3H-GABA binding to rat brain synaptic membranes in vitro have been investigated. The specific binding of 3H-GABA displays saturation kinetics. Only one single population of receptor sites was found (Km = 31.3 nM) with a concentration of 2.09 pmol/mg protein. Only GABA agonists show inhibitory effect on the binding, whereas GABA antagonists, GABA-uptake inhibitors, and inhibitors of GAD and GABA-T are without effect. The order of potencies for GABA agonists are: Muscimol greater than GABA greater than or equal to 4,5-dihydromuscimol greater than 3-aminoproprane sulphonic acid greater than isoguvacine greater than THIP greater than 3-hydroxy-GABA greater than imidazol-4-acetic acid. Agonists and antagonists from other neurone systems as well as neuroleptics and benzodiazepines had no or only a very slight potency in the binding test.
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PMID:Characterization of 3H-GABA receptor binding to rat brain synaptosomal membranes: effect of non GABAergic compounds. 22 5

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

In summary, several branched-chain fatty acids appeared to be competitive inhibitors of GABA-T and non-competitive inhibitors of SSADH. These compounds produce an increase in brain GABA level, and for two of these it was shown that the increase differs among various brain areas. An increase of GABA cannot be obtained by inhibition of SSADH. The increase in brain GABA seems to correlate with the anticonvulsant activity of branched-chain fatty acids.
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PMID:GABA transaminase inhibitors. 39 Sep 93

Experimental procedures are described which are believed to yield results that reflect, within certain limits, the in vivo changes of the size of the GABA pool in nerve endings in comparison with those of all other GABA pools. Two irreversible GABA-T inhibitors, vinyl GABA and acetylenic GABA, two GAD inhibitors, 3-mercaptopropionic acid and pyridoxal phosphate glutamyl-gamma-hydrazone, and di-n propylacetate, a clinically useful anticonvulsant, have been studied to determine their effects on GABA compartmentalization in mouse brain cortex. The changes elicited by these drugs in subcellular fractions of brain cortex homogenates support the notion that measurement of amino acid concentrations in crude synaptosomal fractions and in supernatant fractions under controlled conditions allow one to draw conclusions about relative changes of pool sizes in vivo. In particular this work showed that a specific increase in the concentration of GABA within the nerve endings is more important than a large increase of total brain GABA as a means of decreasing susceptibility to a variety of chemically or physically induced seizures.
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PMID:Metabolic inhibitors and subcellular distribution of GABA. 39 22

In order to assess the possible effects of central GABA activation on the consolidation of shock avoidance, the GABA-T inhibitor amino-oxyacetic acid (AOAA) was administered posttrial to adult male rats. Learning was assessed over nine widely spaced sessions of 20 trials each. AOAA-treated animals showed learning within sessions and a lack of consolidation across sessions. Controls, on the other hand, showed learning both within and across sessions. This evidence agrees with previous reports suggesting GABA involvement in memory processes.
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PMID:GABA involvement in memory consolidation: evidence from posttrial amino-oxyacetic acid. 41 70

In young chicks the effects of 3 min stroboscope stimulation on GABA and free glutamic acid content and on GAD and GABA-T activity in optic lobes were studied. A significant depletion in GABA and glutamic acid levels was found to occur. In addition a sustained increase in GABA-T and GAD activity was observed. In conclusion present experiments are in favour of an inhibitory role played by GABA in chick optic tectum during stroboscope stimulation.
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PMID:Light-evoked changes in chick optic lobe GABA system. 45 34

The administration of L-alpha-amino-beta-chloropropionic acid hydroxamide (L-ACPH) to mice brought about an inhibition in GABA-T activity in the brain of the animals, a significant inhibition occurring with dosage levels as low as 0.25 mmol/kg. Minimum levels of GABA-T activity were reached 3 h after administration of the drug. Brain glutamic acid decarboxylase, DOPA decarboxylase and aspartate aminotransferase activities were not altered by the L-ACPH but alanine aminotransferase activity was totally inhibited. Slight changes in structure caused great changes in the potency of the drugs. For example, the elongation of the L-ACPH structure by one carbon, or a change in the configuration of the amino group from L- to D-, caused a significant decrease in GABA inhibition. The chloro and hydroxamide groups were necessary for inhibitory activity. The administration of L-ACPH to mice delayed the onset of drug induced seizures but had a less noticeable effect against maximal electroshock. The addition of L-ACPH to crude extracts from brain, or to preparations of semipurified GABA-T, also inhibited GABA-T activity. Again the development of the inhibition was time-dependent. Possible mechanisms of action with respect to L-ACPH induced inhibition of GABA-T activity are discussed in the light of the data presented.
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PMID:Alteration of GABA metabolism in mammalian brain by l-alpha-amino-beta-chloropropionic acid hydroxamide and related compounds. 45 23

Elevation of brain GABA levels by GABA-T inhibition is accompanied by a decrease of S-adenosylmethionine decarboxylase activity. This is followed by an increase of ornithine decarboxylase activity and a severalfold increase of brain putrescine levels. Spermidine and spermine levels are not significantly affected under these conditions. These unexpected findings support a regulatory interaction between GABA and polyamine metabolism.
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PMID:Regulatory interrelations between GABA and polyamines. I. Brain GABA levels and polyamine metabolism. 48 78


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