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 Gi2α protein (p < 0.05) compared with controls. However, levels of Gi2α protein were similar in both groups. Abstinent alcoholics had a 2.9‐fold increase in Gi2α 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, Gi2α protein, and Gi2α mRNA levels compared with control subjects, but did have a 1.8‐fold increase (p < 0.01) in Gi2α mRNA. Consistent with enhanced Gi2α expression, lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E1‐, 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, Gi2α, may account for this change.