Cellular tolerance to ethanol as membrane adaptation: A review

Current research on cell membrane biochemical and biophysical changes which underlie tolerance is reviewed. What is known about the action of ethanol suggests that cellular tolerance to it is probably attained by normal mechanisms of membrane adaptation. The sites at which membrane properties could be regulated are discussed. Experimental studies of lipid and protein changes in membranes exposed to alcohol are reviewed. Evidence from lower organisms suggests that membrane adaptation is primarily a function of the phospholipids of the membrane lipid bilayer. In more complex mammalian membranes the possibility exists of adaptation in cholesterol or in membrane proteins. Membranes from ethanol-tolerant animals are resistant to the 'fluidising' effects of ethanol in vitro, but there does not seem to be a simple relationship between bulk membrane fluidity and tolerance to alcohol. The activities of several membrane-associated enzymes show tolerance to the effects of ethanol when it is chronically administered; this could be due to changes in the enzyme proteins or in the lipid surrounding them. It is suggested that the ability of mammals to perform these adaptive changes in neuronal membranes (which may be under strong genetic influence and may underlie tolerance and physical dependence) may have important implications for survival under environmental conditions which alter the milieu intérieur.