Metabolic changes after prior treatment with ethanol. Evidence against in involvement of the Na+ + K+-activated ATPase in the increase in ethanol metabolism.

In perfused rat liver, the inhibition of ethanol uptake by ouabain does not follow the rapid inhibition of the Na+ K+- activated ATPase as assessed by changes in perfusate K+] (half-time, t 1/2 = 2--3 min), but correlated rather with the slow inhibition of oxygen uptake (maximal inhibition = 40% in 20 min). The data indicate that ouabain exerts its effect on ethanol metabolism via the following sequence of events; inhibition of the sodium pump is followed gradually by a perturbation of the intracellular cation milieu; this leads to an inhibition of the mitochondrial respiratory chain, resulting in diminished rate of NADH oxidation, which in turn causes in inhibition of ethanol metabolism.