Differential Response of Adenylate Cyclase and ATPase Activities After Chronic Ethanol Exposure of PC12 Cells

Abstract: The direct effects of chronic ethanol administration on adenylate cyclase, Na,K‐ATPase, and Mg‐ATPase activities in a cell containing neuronal characteristics were investigated using PC 12 pheochromocytoma cells. Exposure of PC12 cells to0, 75, and 150 mM ethanol for 4 days caused a dose‐dependent increase in the stimulation of adenylate cyclase by in vitro ethanol without altering activation of the enzyme by GTP, NaF, MnCl₂, or 2‐chloroadenosine. Conversely, a 4‐day treatment with 150 mM ethanol increased Na,K‐ATPase and Mg‐ATPase activities without altering the inhibitory effects of in vitro ethanol. The increase in Na,K‐ATPase activity was associated with an increase in V_max without any change in the K_m for KC1. Chronic ethanol exposure also increased the amount of [³H]ouabain specifically bound to PC 12 cell membranes. Except for the increase in Mg‐ATPase activity, the above results were also observed when chronic ethanol treatment was carried out in the presence of pyrazole. Although ethanol slowed PC 12 cell growth, observed changes were not due to an ethanol‐induced reduction in cellular density. A 4‐day exposure of a nonneuronal cell line (Madin Darby canine kidney cell) to 150 mM ethanol did not alter adenylate cyclase or ATPase activities. The present study indicates that the direct effects of chronic ethanol exposure of a neuronal‐like cell involve an increase in the density of sodium pumps per cell and an enhanced sensitivity of adenylate cyclase to activation by ethanol.