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Efflux of preloaded radioactive gamma‐aminobutyric acid (GABA) from mouse brain fractions enriched in synaptosomes could be significantly and reproducibly increased by switching from Ca 2+ ‐free wash solution to one containing 2 mM‐Ca 2+ . With a filtration apparatus equipped for simultaneous buffer changes of eight samples, effects of various drugs on Ca 2+ ‐dependent and Ca 2+ ‐independent efflux of GABA were studied. Several membrane‐perturbing agents, including imipramine and neuroleptics like haloperidol and chlorpromazine, at 1 μM, potently inhibited Ca 2+ ‐dependent GABA release. Benzodiazepine drugs similarly inhibited Ca 2+ ‐dependent efflux, but also under appropriate conditions, enhanced Ca 2+ ‐independent efflux. Stimulation of Ca 2+ ‐independent efflux was observed with nonradioactive GABA and with GABA analogues which inhibit GABA transport, reflecting exchange of GABA via the high‐affinity transport system. Diazepam was found to inhibit GABA transport (non‐competitively; I 50 , 50 μM); effects on the transport system might be related to observations of potentiated GABA action and anti‐convulsant effects of this drug.
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Olsen et al. (1977) studied this question.
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