Ethanol-induced changes in activities of adenylate cyclase, guanylate cyclase and cyclic adenosine 3′,5′-monophosphate dependent protein kinase in the brain and liver

Abstract

Effects of acute and chronic administrations of ethanol on the activities of adenylate cyclase, guanylate cyclase and cyclic adenosine 3′,5′-monophosphate (cyclic AMP) dependent protein kinase in the mouse brain and liver were investigated. The activities in the cerebral cortex and liver of adenylate cyclase and guanylate cyclase, the enzymes responsible for the formation of cyclic AMP and cyclic GMP (cyclic guanosine 3′,5′-monophosphate), respectively, were not significantly affected by acute ethanol administration. On the other hand, adenylate cyclase activities in the cerebral cortex and liver were activated significantly following continuous administrations of ethanol. In the case of guanylate cyclase, no significant changes in the basal and NaN 3-activated activities were found in the brain, whereas activities in the liver, measured in the presence of NaN 3, were inhibited significantly following continuous administrations of ethanol. The cerebral content of cyclic AMP was also increased significantly following continuous ethanol treatments, while no such change was found in acutely ethanol-treated groups. The stimulatory effect of norepinephrine on the formation of cyclic AMP in slices of the cerebral cortex was significantly attenuated, whereas that of glucagon on hepatic adenylate cyclase activity was significantly increased following continuous administrations of ethanol. The activity of cyclic AMP dependent protein kinase in synaptosomal fractions from the brain was also significantly increased by continuous ethanol treatments. Cerebral and hepatic phosphodiesterase activities, measured in the presence of cyclic AMP or cyclic GMP, were not affected by both acute and continuous administrations of ethanol. Present results indicate that continuous administrations of ethanol induce the activation of cerebral and hepatic adenylate cyclases and the inhibition of NaN 3-activated guanylate cyclase activity in the liver. The possible significance of these findings in the occurrence of ethanol intoxication in the brain and liver is briefly discussed.