REDUCED SENSITIVITY TO ETHANOL OF GS-ALPHA AND GI O-ALPHA IN THE CEREBRAL-CORTEX OF ALCOHOLIC PATIENTS/

In this study, we examined the quantity and quality of G proteins in m embrane preparations from cortical regions (frontal, parietal, tempora l and occipital cortex) in post-mortem brains obtained from subjects w ith chronic alcoholism and controls matched with respect to age and po st-mortem delay (PMDT). Immunoblot analysis showed that the level of G sH alpha (52 kDa) was significantly decreased in temporal cortical mem branes from alcoholics compared with controls, while no differences we re observed in the amount of any G protein in frontal, parietal and oc cipital regions. Additionally, ethanol enhanced photoaffinity guanine nucleotide binding to both Gs alpha and Gi/o alpha in human cortical m embranes. The percentage of increase in ethanol-stimulated photoaffini ty GTP labeling of Gs alpha and Gi/o alpha was decreased in alcoholic patients in all cortical regions. These observations indicated that su bsensitivities to ethanol-induced stimulation in G protein may contrib ute to impaired trans-signaling in cortical membranes of chronic alcoh olics.