Direct action of ethanol on cerebral GABA A receptor complex: Analysis using purified and reconstituted GABA A receptor complex

Abstract

Possible direct action of ethanol on cerebral GABA A receptor complex has been analyzed using reconstituted vesicles with purified GABA A/benzodiazepine receptor/Cl ion channel complex prepared from the bovine cerebral cortex. Addition of ethanol to the reconstituted vesicles with purified GABA A receptor complex induced a significant facilitation of GABA-dependent 36Cl − influx in a dose-dependent manner. Furthermore, the reconstituted vesicles with pretreated GABA A receptor complex with 20 mM ethanol, a dose that had no significant effect on GABA A receptor binding, also exhibited a significant increase of GABA-dependent 36Cl influx as compared with that found in non-treated preparation. On the other hand, the facilitation of GABA-dependent 36Cl − influx by flunitrazepam was found to be eliminated by the ethanol pretreatment. The present results suggest that ethanol may affect directly on GABA A receptor complex and facilitate the function of Cl ion channel but eliminate or decrease the functional coupling between benzodiazepine receptor and GABA A receptor.