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A number of data suggest that the chronic ethanol treatment induces derangements of cell membrane structure leading to modifications of membrane related processes. In particular, alterations have been observed in the mechanisms of neurotransmitter recognition and in the coupling of the receptor with the effector system. Phosphorylation of specific proteins by cyclic AMP stimulated protein kinases represent the final step in the biological response in several distinct functional processes. Ethanol neurotoxic action therefore may affect neurotransmitter availability and release as well as receptors effector systems and protein phosphorylation. In this line, chronic ethanol treatment in rats decreases cyclic AMP dependent protein kinase activity in rat striatal membrane fractions. When lysine rich histone type III was used as exogenous substrate, cyclic AMP stimulated 32P incorporation was still decreased in the ethanol group. These data favor the hypothesis of a decreased capability of the enzyme to phosphorylate in response to cAMP.

Endogenous protein phosphorylation by cyclic AMP-dependent protein kinase was found reduced in striatal membranes obtained from chronic ethanol-treated rats. Experiments using an exogenous substrate show that the decreased response is due to a deficiency in the phosphorylating activity of the cyclic AMP-dependent protein kinase and not to a lack of endogenous substrate for phosphorylation.

Calcium and calcium-calmodulin dependent phosphorylation of several protein bands was found altered in synaptosomal membranes prepared from ethanol treated rats. The ethanol induced effect on Ca++ and Ca++-calmodulin phosphorylation presented regional differences. In particular 32P incorporation was lower in the striatum and cerebellum, higher in the hippocampus and unmodified in the cortex. Part of the phosphorylated bands had an apparent molecular weight similar to that of the phosphoproteins involved in neurotransmission. These results extend previous observations indicating that calcium movement control is modified during chronic ethanol consumption and suggest that ethanol may interfere at various steps in the calcium-promoted events.