Alterations of receptor-G protein-adenylyl cyclase coupling in alcoholics.

This study investigated alterations in the receptor adenylyl cyclase system in the brain and platelets of alcoholics through the study of GTP binding (G) protein, which has a key role in the system, in the membranes of the post-mortem brain and platelets. Quantitative examination of G protein by immunoblotting showed that GsH alpha in the temporal cortex of the post-mortem alcoholic brain was significantly decreased with controls. Moreover, the extent of ethanol enhancement of functional photoaffinity GTP(azidoanilido GTP) labeling to Gs alpha and Gi alpha was decreased in all cortical regions (frontal, temporal, parietal, occipital cortex) from alcoholics. In the platelet membrane, a quantitative reduction in GsH alpha and GsL alpha levels as assessed by immunoblotting was seen in family history positive (FHP) alcoholics. A reduction in ethanol enhancement of AAGTP labeling to Gs alpha and Gi alpha was also observed in the FHP group. These alterations of G protein were not found in the platelets from family history negative (FHN) alcoholics. The dysfunctions of Gs protein occurring in platelet membranes of the FHP group are likely to parallel those that occur in the alcoholic brain. These results suggest that disturbances of G protein-mediated signal transduction may be involved in the pathophysiology of alcoholics and that platelet G protein may be used as a trait marker of alcoholics.