Two receptors for cardiac glycosides in the heart

  • E. Erdmann
  • L. Brown
  • K. Werdan


Specific binding of 3H-ouabain to rat cardiac cell membranes revealed a high affinity and a low affinity site. In order to test the pharmacological significance of these different types of binding sites, specific 3H-ouabain binding, force of contraction and 86Rb+-uptake were measured simultaneously in contracting cat papillary muscles and in guinea pig atria.

The results in the digitalis sensitive cat shows one type of cardiac glycoside receptors with high affinity (KD~10-7M) for ouabain. The occupation of this receptor runs parallel with an increase in force of contraction and an inhibition of 86Rb+-uptake. In the rather digitalis insensitive guinea pig, 3H-ouabain binding also runs parallel with increased force of contraction, 86Rb+-uptake, however, is only inhibited at toxic glycoside concentrations. Thus, in rat and guinea pig heart there exist at least two different digitalis receptors - the high affinity receptor seems to be coupled to inotropic effects, the low affinity receptor is linked to inhibition of (Na++K+)-ATPase.

Key words

3H-ouabain cardiac glycoside receptors (Na++K+)-ATPase positive inotropy. 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Akera T, Brody TM (1978) The Role of Na+, K+-ATPase in the Inotropic Action of Digitalis. Pharmacol Rev 29: 187–219Google Scholar
  2. 2.
    Akera T, Yamamoto S, Temma K, Kim DH, Brody TM (1981) Is ouabain-sensitive rubidium or potassium uptake a measure of sodium pump activity in isolated cardiac muscle? Biochim Biophys Acta 640: 779–790PubMedCrossRefGoogle Scholar
  3. 3.
    Brown L, Werdan K, Erdmann E (1983) Consequences of specific 3H-ouabain binding to guinea pig left atria and cardiac cell membranes. Biochem Pharmacol 32: 423–435PubMedCrossRefGoogle Scholar
  4. 4.
    Erdmann E, Philipp G, Scholz H (1980) Cardiac glycoside receptor, (Na++K+)-ATPase activity and force of contraction in rat heart. Biochem Pharmacol 29: 3219–3229PubMedCrossRefGoogle Scholar
  5. 5.
    Erdmann E Influence of cardiac glycosides on their receptor, in: Handbook of experimental pharmacology, Vol. 56/1 by Springer-Verlag Berlin, Heidelberg, New York 1981Google Scholar
  6. 6.
    Erdmann E, Philipp G, Scholz H (1981) Evidence for two receptors for cardiac glycosides in the heart in: Cell membrane in function and dysfunction of vascular tissue, edit.: Godfraind T, Meyer P (Elsevier North-Holland, Amsterdam, New York, Oxford ) 76–83Google Scholar
  7. 7.
    Ghysel-Burton J, Godfraind T (1979) Stimulation and inhibition of the sodium pump by cardioactive steroids in relation to their binding sites and their inotropic effect on guinea-pig isolated atria. Br J Pharmac 66: 175–184CrossRefGoogle Scholar
  8. 8.
    Lechat P, Malloy CR, Smith TW (1983) Active transport and inotropic state in guinea pig left atrium. Circ Res 52: 411–422PubMedCrossRefGoogle Scholar
  9. 9.
    Lee CO, Dagostino M (1982) Effect of strophanthidin on intracellular na ion activity and twitch tension of constantly driven canine cardiac purkinje fibers. Biophys J 40: 185–198PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Michael L, Schwartz A, Wallick E (1979) Nature of the transport adenosine triphosphatase digitalis complex: XIV. Inotropy and cardiac glycoside interaction with Na+,K+-ATPase of isolated cat papillary muscles. Molec Pharmacol 16: 135–146Google Scholar
  11. 11.
    Noble D (1980) Mechanism of action of therapeutic levels of cardiac glycosides. Cardiovasc Res 14: 495–514PubMedCrossRefGoogle Scholar
  12. 12.
    Schwartz A (1976) Sodium - potassium adenosine triphosphatase - a receptor for digitalis? Biochem Pharmacol 25: 237–239PubMedCrossRefGoogle Scholar
  13. 13.
    Skou JC (1965) Enzymatic basis for active transport of Na+ and K+ across cell membrane. Rev Physiol 45: 596–617Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • E. Erdmann
    • 1
  • L. Brown
    • 1
  • K. Werdan
    • 1
  1. 1.Medizinische Klinik Ider Universität Klinikum GroßhadernMünchen 70Germany

Personalised recommendations