(Na+,K+)-ATPase and noradrenergic function: effects of chronic ethanol

The experiments in this paper examined interactions between ethanol and repeated noradrenergic stimulation in vivo on regulation of (Na+,K+)-ATPase. The increase in ouabain binding and K+-phosphatase activity associated with (Na+,K+)-ATPase in rats treated with repeated yohimbine injections was prevented by chronic ethanol. Ethanol did not affect the yohimbine-induced alterations in noradrenergic receptor binding or in content of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol, showing that prevention of noradrenergic stimulation of (Na+,K+)-ATPase was not caused by a decrease in availability of norepinephrine. In addition, norepinephrine depletion with the neurotoxin DSP4 did not prevent the increases in (Na+,K+)-ATPase indices during chronic ethanol treatment, showing that they did not result from increased norepinephrine exposure. These results suggest that chronic ethanol reduces sensitivity of (Na+,K+)-ATPase to norepinephrine in vivo, possibly as a consequence of membrane effects of ethanol tolerance.