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Augmentation of ouabain sensitivity of rat liver Na/K-ATPase by in vivo adenovirus-mediated expression of the Na/K-ATPase α2 subunit

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
405
Issue
1
Identifiers
DOI: 10.1016/s0014-5793(97)00087-2
Keywords
  • Gene Therapy
  • Cell Membrane
  • Dna
  • Recombinant
  • Cardiac Glycosides
  • Adenoviridae
Disciplines
  • Biology
  • Chemistry
  • Pharmacology

Abstract

Abstract These are the first experiments to study the effect of in vivo expression of the Na/K-ATPase α2 subunit which serves as a receptor for cardiac glycosides. The α2 subunit is not normally expressed in rat liver, so hepatocytes which lack endogenous α2 protein are a logical first target to study the effects of α2 expression on membrane Na/K-ATPase activity. At 3 days after α2 adenovirus vector infusion, Wistar rat livers contained α2 DNA, α2 mRNA, and α2 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 α2 activity represented 10% of the total active Na/K-ATPase sites in α2 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. © 1997 Federation of European Biochemical Societies.

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