The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin

https://doi.org/10.1016/0006-291X(92)91593-FGet rights and content

Abstract

Digoxin, a widely used cardiac glycoside with a low therapeutic index, is known to interact with a large and diverse group of co-administered drugs, frequently leading to toxic accumulation of the glycoside. Establishing the mechanism(s) of these interactions, therefore, has potential clinical significance. The present studies implicate P-glycoprotein, the MDR1 gene product overexpressed in multidrug resistant cells, as the apical membrane protein responsible for the renal secretion of digoxin and provide an explanation for the occurrence of digoxin toxicity in the presence of certain co-administered medications. Since digoxin is considered a prototype for endogenous digitalis-like glycosides, the results also allow for speculation that endogenous digitalis-like glycosides may be the natural substrates for P-gp.

References (27)

  • M. Bradford

    Analyt. Biochem

    (1976)
  • H. Goldberg et al.

    Biochem. Biophys. Res. Commun

    (1988)
  • J.-P. Jaffrézou et al.

    J. Biol. Chem

    (1991)
  • M. Horio et al.

    Biochim. Biophys. Acta

    (1990)
  • F.S. Labella et al.

    TiPS

    (1989)
  • C.-P.H. Yang et al.

    J. Biol. Chem

    (1989)
  • J.H.M. Charuk et al.

    Biochem. Biophys. Res. Commun

    (1992)
  • W.D. Hager et al.

    New. Engl. J. Med

    (1979)
  • G. Koren et al.

    J. Pharmacol. Exp. Ther

    (1988)
  • K. Schenck-Gustafsson et al.

    Clin. Physiol

    (1982)
  • K.E. Pederson et al.

    Clin. Pharmacol. Ther

    (1981)
  • G. Koren et al.

    Can. J. Physiol. Pharmacol

    (1983)
  • M.S. O'Brien et al.

    J. Pharmacol. Exp. Ther

    (1985)
  • Cited by (0)

    View full text