Effects of ethanol on Arrhenius parameters and activity of mouse striatal adenylate cyclase

Arrhenius plots of basal and dopamine (DA)-stimulated adenylate cyclase activities exhibited discontinuities at 20 degrees, while the plot of fluoride-stimulated adenylate cyclase activity was linear over the studied temperature range. None of the Arrhenius parameters were altered by in vitro addition of ethanol (75 or 750 mM) to enzyme assay mixtures, and Arrhenius parameters were found to be unchanged when enzyme obtained from animals rendered tolerant to, and physically dependent on, ethanol was assayed. The differences between the response to ethanol of adenylate cyclase and the response of other membrane-bound enzymes [e.g. (Na+-K+)ATPase], as measured by Arrhenius plots, may indicate different sites of action of ethanol. When the specific activity of adenylate cyclase was examined, ethanol was found to stimulate activity at all temperatures tested. The dose-response curve for ethanol activation of basal adenylate cyclase activity was shifted to the right for enzyme obtained from mice chronically treated with ethanol. Analysis of the data indicated that activation of adenylate cyclase by ethanol (as well as by DA) was an entropy-driven process. Since ethanol treatment did not affect the Arrhenius parameters, which appear to be associated with membrane lipids, it is suggested that enzyme activation by ethanol results from direct effects on the enzyme or regulatory protein. Resistance to this effect occurs through changes in protein conformation following chronic ethanol treatment.