ENHANCED EXPRESSION OF THE INHIBITORY PROTEIN GI2-ALPHA AND DECREASEDACTIVITY OF ADENYLYL CYCLASE IN LYMPHOCYTES OF ABSTINENT ALCOHOLICS

Ethanol exposure alters signal transduction through the adenylyl cycla se (AC) system. To elucidate the basis for this effect, we investigate d the AC system in peripheral lymphocytes from abstinent alcoholic men (n = 22), actively drinking alcoholic men (n = 41), and nonalcoholic control men (n = 16). Immunoblot analysis of lymphocyte membranes from abstinent alcoholics demonstrated a 3.0-fold increase in the level of G(i2)alpha protein (p < 0.05) compared with controls. However, levels of G(s)alpha protein were similar in both groups. Abstinent alcoholic s had a 2.9-fold increase in G(i2)alpha mRNA (p < 0.001) and a 2.7-fol d increase in G(i2)a mRNA (p < 0.03) compared with lymphocytes from co ntrol subjects. Actively drinking alcoholics, in contrast, had unalter ed G(s)alpha protein, G(i2)alpha protein, and G(i2)alpha mRNA levels c ompared with control subjects, but did have a 1.8-fold increase (p < 0 .01) in G(s)alpha mRNA. Consistent with enhanced G(i2)alpha expression , lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E1-, guanosine 5'-O-(3-thiotriphosphate)-gammaS-, and fo rskolin-stimulated AC activity compared with both controls and activel y drinking alcoholics (p < 0.05). We conclude that lymphocyte AC is re duced during abstinence from alcohol and enhanced expression of the in hibitory G-protein, Gi2alpha, may account for this change.