Effect of aminooxyacetic acid (AOAA) on GABA levels in some parts of the rat brain.
The accumulation of GABA in the cerebellum and medulla oblongata-pons of rats has been studied after inhibition of GABA-T (EC 2.6.1.19) by different doses of AOAA. It was found that intraperitoneal (i.p.) injections of AOAA were, at least during the first hour after injection, much less effective than intravenous (i.v.) injections probably due to poor absorption i.p. After i.v. injection, AOAA caused a maximal accumulation of GABA in the cerebellum at a dose of 50 mg/kg. This maximal effect was virtually unchanged up to a dose of 150 mg/kg (the highest dose tested i.v.). If GAD (EC 4.1.1.15) was inhibited by 3-mercaptopropionic acid 30 min after AOAA (90 mg/kg i.v.) the GABA level was stable for at least another 30 min. The rate of GABA accumulation in the cerebellum during the first 15 min after AOAA (50-150 mg/kg i.v.) was 0.086 mumol/g/min and thereafter 0.034 mumol/g/min. It is concluded that AOAA in vivo in a wide dose range inhibits GABA-T almost 100% without affecting GAD to any great extent, and that the onset of action is rapid after i.v. but not after i.p. injection.
D015097:3-Mercaptopropionic Acid / Q000378:metabolism; D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D011149:Pons / Q000378:metabolism; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; D015097:3-Mercaptopropionic Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase