Aminooxyacetic acid induced changes in γ-aminobutyrate metabolism at the subcellular level

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Abstract
Aminooxyacetic acid (AOAA) (0.1 or 0.23 mmol/kg) was administered to mice which were killed 1.5 and 6 h after treatment. Synaptosomal- and mitochondrial-enriched fractions were obtained by conventional ultracentrifugation procedures. The γ-aminobutyric acid (GABA) content of the synaptosomal fraction was elevated by previous treatment of the mice with AOAA, the increase being greater at 6 h than at 1.5 h posttreatment. This finding suggested that a transient elevation of the GABA content of nerve endings was not responsible for the fast-developing anticonvulsant action of AOAA. The activity of aminobutyrate aminotransferase (GABA-T) was inhibited after AOAA treatment, the degree of inhibition being greater in the mitochondrial-enriched than in the synaptosomal-enriched fraction. Evidence for circadian changes in GABA-T activity was obtained. The limitations and advantages of subcellular fractionation techniques in determining the effects of drugs on GABA metabolism were assessed.