AN ANESTHETIC DOSE OF ETHANOL INHIBITS CYCLIC-AMP FORMATION BY ALTERING THE FUNCTION OF G(S) PROTEIN

The effects of ethanol on cerebral gamma-aminobutyric acid (GABA)(B) r eceptor and its related signal transduction systems were studied. [H-3 ]GABA binding to cerebral GABAB receptors in crude synaptic membranes from rat brain was unaffected by ethanol at concentrations up to 100 m M, although 100 mM ethanol suppressed not only the basal but also fors kolin-stimulated cAMP formation in cerebral cortical membrane vesicles . The suppressive effect of baclofen and the stimulatory effect of for skolin on cAMP formation was also found to be unaltered by ethanol. Pr etreatment of the membrane vesicles with islet-activating protein (IAP ), which eliminates the function of Gi protein by its ribosylation, ha d no effect on the suppressive effects of ethanol on basal and forskol in-stimulated cAMP formation. In contrast, pretreatment of membrane ve sicles with 'low pH', which is known to suppress the function of G(s) protein, eliminated the suppressive effect of ethanol on cAMP formatio n. These results suggest that an anaesthetic dose of ethanol, which is below that necessary to cause changes in receptor binding, may not af fect the functions of GABA(B)/G(i), G(o) protein/adenylate cyclase sys tem, but suppresses cAMP formation systems which are coupled with G(s) protein.