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

Slice preparations of rat cuneate nucleus were used for studies on the gamma-aminobutyric acid GABAA-receptor complex following chronic and acute pretreatment with GABA-alpha-ketoglutarate aminotransferase (GABA-T) inhibitors. The whole brain GABA concentration was significantly increased 2.9 fold and 2.6 fold following treatment with ethanolamine O-sulphate (EOS, orally) for 15-30 days and 56-64 days, respectively. One hour after a single injection of gamma-acetylenic GABA (GAG) i.p., there was a significant 2.1 fold increase in whole brain GABA. Superfusion of a slice with muscimol or the GABA uptake inhibitor nipecotic acid depolarized the afferent nerve fibres. These effects were potentiated by flurazepam (1 microM) and pentobarbitone (10 microM) and antagonized by picrotoxin (3 microM, 30 microM). Following 15-30 days of EOS-treatment, the depolarization response to muscimol was decreased and that to nipecotic acid increased. These changes were no longer significant by 56-64 days of pretreatment. The acute dose of GAG did not affect the depolarization response to muscimol but increased that to nipecotic acid. The potentiations of muscimol by flurazepam (1 microM) and pentobarbitone (10 microM) were enhanced following chronic EOS treatment (15-64 days). The enhancement of flurazepam was less after 56-64 days than after 15-30 days pretreatment whereas the enhancement of pentobarbitone was similar at both times. Acute GAG treatment had no effect. The potency of picrotoxin as an antagonist of muscimol was reduced following chronic EOS treatment; the enhancement was less after 56-64 days than after 15-30 days pretreatment. Acute GAG treatment caused only a very small reduction in picrotoxin potency. Possible adaptations in the GABAA-receptor complex and its modulation during chronic elevation of brain GABA are discussed.
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PMID:Adaptation of the GABAA-receptor complex in rat brain during chronic elevation of GABA by ethanolamine O-sulphate. 303 47

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