Augmentation of ouabain sensitivity of rat liver Na/K-ATPase by in vivo adenovirus-mediated expression of the Na/K-ATPase alpha 2 subunit

These are the first experiments to study the effect of in vivo expression of the Na/K-ATPase alpha 2 subunit which serves as a receptor for cardiac glycosides, The alpha 2 subunit is not normally expressed in rat liver, so hepatocytes which lack endogenous alpha 2 protein are a logical first target to study the effects of alpha 2 expression on membrane Na/K-ATPase activity, At 3 days after alpha 2 adenovirns vector infusion, Wistar rat livers contained alpha 2 DNA, alpha 2 mRNA, and alpha 2 protein, Rat liver membrane ouabain binding activity and the sensitivity of Na/K-ATPase activity to ouabain significantly increased, Total membrane Na/K-ATPase was regulated at a constant level while expressed alpha 2 activity represented 10% of the total active Na/K-ATPase sites in alpha 2 transduced rat liver, These studies are the first to establish a paradigm in which an endogenous drug receptor is expressed to alter cellular pharmacologic sensitivity. (C) 1997 Federation of European Biochemical Societies.