It has been suggested that ethanol stimulates adenylate cyclase in vitro through an increased function of Ns, the activitory component of adenylate cyclase. Because of the interaction of Ns with Ni, the adenylate cyclase inhibitory component, we have studied the effect of ethanol (0.05–0.2 M) on Ni-mediated adenylate cyclase inhibition caused by the adenosine analog N 6-phenylisopropyladenosine (N6-PIA) in brain cortical membranes. Ethanol did not alter N6-PIA binding to the adenosine Ri-receptors, stimulated slightly basal adenylate cyclase activity but abolished adenylate cyclase inhibition due to N6-PIA, suggesting an effect of ethanol on the inhibitory coupling pathway. This was further supported by loss of the adenylate cyclase inhibitory response to GTP (10−5 M). It thus seems that, besides its effect on the Ns system, ethanol may also impair Ni-mediated adenylate cyclase responses in rat cerebral cortex.
