DIFFERENTIAL EXPRESSION OF GUANOSINE TRIPHOSPHATE-BINDING PROTEINS INMEN AT HIGH AND LOW-RISK FOR THE FUTURE-DEVELOPMENT OF ALCOHOLISM

We evaluated G-proteins that are components of adenylyl cyclase (AC) s ignal transduction in erythrocyte and lymphocyte membranes from 26 fam ily history positive (FHP) nonalcoholic and 26 family history negative (FHN) nonalcoholic subjects. Subjects were classified as FHP if their father met criteria for alcohol dependence; as FHN, if there was no h istory of alcoholism in any first or second degree relatives. Immunobl ot analysis indicated that levels of erythrocyte membrane Gs alpha fro m FHP subjects were greater than levels in FHN subjects (171+/-11 vs 1 00+/-6, P < 0.001). To confirm the results of the immunoblot analysis, Gs alpha was quantitated by cholera toxin-dependent [P-32]ADP-ribosyl ation. Levels of erythrocyte [P-32]ADP-ribose-Gs alpha from FHP subjec ts were greater than levels in FHN subjects (236+/-28 vs 100+/-14, P < 0.001). Gs alpha levels did not correlate with age or alcohol consump tion. By contrast to differences in Gs alpha, immunoblot analysis show ed similar levels of Gi(2)alpha and Gi(3)alpha in erythrocyte membrane s of FHP and FHN subjects. Pertussis toxin-catalyzed [P-32]ADP-ribosyl ation of Gi-like G-proteins confirmed the immunoblot observations. Las tly, compared to FHN subjects, FHP subjects had enhanced Gs alpha expr ession in lymphocyte membranes as well (138+/-1l vs 100+/-5.5; P < 0.0 2). In summary, compared to FHN nonalcoholic men, FHP nonalcoholic men had greater levels of the stimulatory G-protein, Gs alpha, in erythro cyte and lymphocyte membranes. Enhanced expression of Gs alpha may be a marker of increased risk for the future development of alcoholism.