Platelet adenylyl cyclase activity as a biochemical trait marker for predisposition to alcoholism.
Previous studies demonstrated a reduced Gs-protein stimulated adenylyl cyclase activity in the brain and blood cells of alcoholics. We investigated this phenomenon in platelets of children of alcoholics (COA), i.e., of children at high risk for the acquisition of alcoholism and (as yet) not regularly consuming alcohol. Gs-protein mediated stimulation of adenylyl cyclase by 30 mM NaF and 50 microM forskolin stimulated adenylyl cyclase activity were assessed in platelet membranes of 23 (male and female) COA and 20 control children. Gs-protein stimulated cAMP production by NaF, unlike that induced by direct stimulation of adenylyl cyclase with forskolin, in platelet membranes of COA was profoundly lower than in platelet membranes of control children. Moreover, such a reduced Gs-protein functioning was only observed in platelet membranes of COA with a multigenerational family history of alcoholism. A reduction of Gs-protein stimulated adenylyl cyclase activity in platelets may represent a sensitive and gender-independent trait marker for predisposition to alcoholism, rather than a state marker for alcoholism.
Ratsma
J E
JE
Department of Child and Adolescent Psychiatry, University of Amsterdam, The Netherlands.
Gunning
W B
WB
Leurs
R
R
Schoffelmeer
A N
AN
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000293:Adolescent; D000437:Alcoholism / Q000235:genetics*; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D002648:Child; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D012969:Sodium Fluoride / Q000494:pharmacology
D015415:Biomarkers; D005576:Colforsin; D012969:Sodium Fluoride; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases