Enhanced Expression of the Inhibitory Protein Gi2α and Decreased Activity of Adenylyl Cyclase in Lymphocytes of Abstinent Alcoholics

Ethanol exposure alters signal transduction through the adenylyl cyclase (AC) system. To elucidate the basis for this effect, we investigated 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_i2α protein ( p < 0.05) compared with controls. However, levels of G_i2α protein were similar in both groups. Abstinent alcoholics had a 2.9-fold increase in G_i2α mRNA ( p < 0.001) and a 2.7-fold increase in G₂α mRNA ( p < 0.03) compared with lymphocytes from control subjects. Actively drinking alcoholics, in contrast, had unaltered G₂α protein, G_i2α protein, and G_i2α mRNA levels compared with control subjects, but did have a 1.8-fold increase ( p < 0.01) in G_i2α mRNA. Consistent with enhanced G_i2α expression, lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E_1-, guanosine 5'-0-(3-thiotriphosphate)-γS-, and forskolin-stimulated AC activity compared with both controls and actively drinking alcoholics ( p < 0.05). We conclude that lymphocyte AC is reduced during abstinence from alcohol and enhanced expression of the inhibitory G-protein, G_i2α, may account for this change.