Platelet adenylyl cyclase activity as a biochemical trait marker for predisposition to alcoholism

Previous studies demonstrated a reduced G(s)-protein stimulated adenylyl cy clase activity in the brain and blood cells of alcoholics. We investigated this phenomenon in platelets of children of alcoholics (COA), i.e., of chil dren at high risk for the acquisition of alcoholism and (as yet) not regula rly consuming alcohol. G(s)-protein mediated stimulation of adenylyl cyclas e by 30 mM NaF and 50 mu M forskolin stimulated adenylyl cyclase activity w ere assessed in platelet membranes of 23 (male and female) COA and 20 contr ol children. G(s)-protein stimulated cAMP production by NaF, unlike that in duced by direct stimulation of adenylyl cyclase with forskolin, in platelet membranes of COA was profoundly lower than in platelet membranes of contro l children. Moreover, such a reduced G(s)-protein functioning was only obse rved in platelet membranes of COA with a multigenerational family history o f alcoholism. A reduction of G(s)-protein stimulated adenylyl cyclase activ ity in platelets may represent a sensitive and gender-independent trait mar ker for predisposition to alcoholism, rather than a state marker for alcoho lism.