Chronic ethanol treatment affects synaptosomal membrane-bound enzymes.

A progressive increase in activity of some brain membrane-bound enzymes is shown after 2 and 4 weeks of ethanol administration. After 4 weeks the activities in brain homogenate of (Na+, K+) ATPase, Ca++ ATPase, 5'-nucleotidase, acetylcholinesterase and adenylate cyclase increased 150, 200, 140, 125 and 129 percent, respectively. Arrhenius plots of synaptosomal (Na+, K+) ATPase and acetylcholinesterase from alcohol-treated rats showed a lower transition temperature than control rats after two weeks, and this changed to a higher transition temperature after 4 and 8 weeks. Also, when ethanol was added in vitro to the control membranes, the transition temperature was lowered. However, if the alcohol was added to the membranes from alcohol-treated animals, the transition temperature was lowered to a value similar to that of controls. Fluorescence studies with l-anilinonaphthalene-8-sulfonate (ANS) demonstrate that ethanol induces a decrease in the fluorescence of ANS bound to brain synaptic membranes. This decrease in fluorescence is less than when these membranes are derived from chronically ethanol-treated rats. Also, when the synaptosomal enzymes were exposed to exogenous agents such as detergents, the enzyme obtained from alcohol-treated rats was more stable than that from control rats. These findings indicate a protein conformation change, probably due to the alteration of the physical properties of membrane lipids following chronic ethanol administration. These findings also demonstrate that there is a resistance to the effect of ethanol in membranes of animals habituated to ethanol that may be related to the adaptative modifications that underlie tolerance to and physical dependence on alcohol.