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Subclassification of cardiac glycoside receptors

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Cardiac Glycoside Receptors and Positive Inotropy

Abstract

It is widely accepted that cardiac glycosides are therapeutically efficient to treat heart failure. Their beneficial action may be attributed to their positive inotropic effect, even if their action on preload and afterload has to be taken into account (12). Despite of the large interest devoted to these drugs, the mechanism of their inotropic action is still a matter of controversy. In 1953, Schatzman reported that cardiac glycosides inhibit the ionic restoration of red blood cells occurring during rewarming after an incubation at low temperature which altered the physiological distribution of Na and K. This observation showed that the glycosides alter the transport of monovalent cations against their electrochemical gradient. In 1957, Skou discovered Na,K-ATPase and since, the mechanism of Na and K transport has been extensively investigated. Several physiological processes are coupled to the Na,K-pump, the identification of this coupling has been demonstrated by blockade of the pump by large doses of cardiac glycosides.

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References

  1. Adams RJ, Schwartz A, Grupp G, Grupp IL, Lee, SW, Wallick ET, Powell T, Twist VW, Gathiram P (1982) High-affinity ouabain binding site and low-dose positive inotropic effect in rat myocardium. Nature 296: 167–169

    Article  CAS  PubMed  Google Scholar 

  2. Akera T (1981) Effects of cardiac glycosides on (Na + K)-ATPase. In: Cardiac Glycosides, Handb. Exp Pharm Vol 56/1, pp 287–383, Greeff K (Ed) Springer-Verlag, Berlin Heidelberg New York

    Google Scholar 

  3. Castaneda H. G, Godfraind T (1984) Effect of high sodium intake on tissue distribution of endogenous digitalis-like material in the rat. Clin Sei 66: 225–228

    Google Scholar 

  4. Cohen I, Daut J, Noble D (1976) An analysis on the action of low concentrations of ouabain on membrane currents in Purkinje fibres. J Physiol (London) 260: 75–103

    CAS  Google Scholar 

  5. Deitmer JW, Ellis D (1970) The intracellular sodium activity of cardiac Purkinje fibres during inhibition and reactivation of the Na/K pump. J Physiol (London) 284: 241–259

    Google Scholar 

  6. De Pover A., Godfraind T (1979) Interaction of ouabain with (Na + K)-ATPase from human heart and from guinea-pig heart. Biochem Pharmacol 28: 3051–3056

    Article  PubMed  Google Scholar 

  7. Erdmann E, Schoner W (1973) Ouabain-receptor interactions in (Na + K)-ATPase preparations. II. Effect of cations and nucleotides on rate constants and dissociation constants. Biochim Biophys Acta 330: 302–315

    Article  CAS  PubMed  Google Scholar 

  8. Erdmann E, Philipp G, Scholz H (1980) Cardiac glycoside receptor, (Na + K)-ATPase activity and force of contraction in rat heart. Biochem Pharmacol 29: 3219–3229

    Article  CAS  PubMed  Google Scholar 

  9. Finet M, Godfraind T, Noel F (1983) The inotropic effect of ouabain and its antagonism by dihydroouabain in rat isolated atria and ventricles in relation to specific binding sites. Br J Pharmac 80: 751–759

    Article  CAS  Google Scholar 

  10. Ghysel-Burton J, Godfraind T (1977) High and low affinity ouabain binding sites in guinea-pig atria. Br J Pharmac 498 P

    Google Scholar 

  11. 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: 175–184

    Article  CAS  Google Scholar 

  12. Godfraind T (1973) The therapeutic mode of action of cardiac glycosides. Arch int Pharmacodyn Ther 206: 384–388

    CAS  PubMed  Google Scholar 

  13. Godfraind T (1975) Cardiac glycoside receptors in the heart. Biochem Pharmacol 24: 823–827

    Article  CAS  PubMed  Google Scholar 

  14. Godfraind T (1980) Stimulation et inhibition de la pompe ä sodium par les heterosides cardiotoni- ques. Bull Acad Roy Med Belg 135: 174–192

    CAS  Google Scholar 

  15. Godfraind T (1982) Stimulation and inhibition of the Na, K-pump by cardiac glycosides. In: “Cardiac Glycosides” Greef K Ed Handb. Exp Pharm, Vol 56/1, pp 381 - 393. Springer-Verlag, Berlin Heidelberg New York

    Google Scholar 

  16. Godfraind T, Ghysel-Burton J (1977) Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump. Nature 265: 165–166

    Article  CAS  PubMed  Google Scholar 

  17. Godfraind T, Ghysel-Burton J (1979) The cardioactive properties of SC4453, a digoxin analogue with a C17 ß-pyridazine ring. Eur J Pharmacol 60: 337–344

    Article  CAS  PubMed  Google Scholar 

  18. Godfraind T, Ghysel-Burton J (1980) Independence of the positive inotropic effect of ouabain from the inhibition of the heart Na/K pump. Proc Natl Acad Sei USA 77: 3067–3069

    Article  CAS  Google Scholar 

  19. Godfraind T, Ghysel-Burton J, De Pover A (1982) Dihydroouabain is an antagonist of ouabain inotropic action. Nature 299: 824–826

    Article  CAS  PubMed  Google Scholar 

  20. Godfraind T, De Pover A, Tona Lutete D-N (1980) Identification with potassium and vanadate of two classes of specific ouabain binding sites in a (Na + K)-ATPase preparation from the guinea-pig heart. Biochem Pharmacol 29: 1195–1199

    Article  CAS  PubMed  Google Scholar 

  21. Godfraind T, De Pover A, Castaneda Hernandez, Fagoo M (1982) Cardiodigin endogenous digitalis¬like material from mammalian heart. Arch int Pharmacodyn Ther 258: 165–167

    CAS  PubMed  Google Scholar 

  22. Grupp G, Grupp IL, Ghysel-Burton J, Godfraind T, Schwartz A (1982) Effects of very low concentrations of ouabain on contractile force of isolated guinea-pig, rabbit and cat atria and right ventricular papillary muscles: an interinstitutional study. J Pharmacol Exp Ther 220: 145–151

    CAS  PubMed  Google Scholar 

  23. Hart G, Noble D, Shimoni Y (1983) The effects of low concentrations of cardiotonic steroids on membrane currents and tension in sheep Purkinje fibres. J Physiol (London) 334: 103–131

    CAS  Google Scholar 

  24. Hougen TJ, Spicer N, Smith TW (1981) Stimulation of monovalent cation active transport by low concentrations of cardiac glycosides. Role of catecholamines. J Clin Invest 68: 1207–1214

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Langer GA (1983) The sodium pump lag revisited. J Mol Cell Cardiol 15: 647–651

    Article  CAS  PubMed  Google Scholar 

  26. Lechat P, Mallory CR, Smith TW (1983) Active transport and inotropic state in guinea-pig left atrium. Circ Res 52: 411–422

    Article  CAS  PubMed  Google Scholar 

  27. Matsui H, Schwartz A (1966) Kinetic analysis of ouabain-K and Na interaction on a Na, K-dependent adenosine triphosphatase from cardiac tissue. Biochem Biophys Res Commun 25: 147–152

    Google Scholar 

  28. Noble D (1980) Mechanism of action of therapeutic levels of cardiac glycosides. Cardiovascular Res 14: 495–514

    Article  CAS  Google Scholar 

  29. Noel F, Godfraind T (1984) Heterogeneity of ouabain specific binding sites and (Na + K)-ATPase inhibition in microsomes from rat heart. Biochem Pharmacol, 33: 47–53

    Article  CAS  PubMed  Google Scholar 

  30. Repke K (1963) Metabolism of cardiac glycosides. In: “Proceedings of the First International Pharmacological Meeting ”, Repke K Ed pp 47–74 ( Pergamon Press New York )

    Google Scholar 

  31. Reuter H (1974) Exchange of calcium ions in the mammalian myocardium. Mechanisms and physiological significance. Circ Res 34: 599 - 605

    Article  PubMed  Google Scholar 

  32. Schatzmann HJ (1953) Herzglycoside als Hemmstoffe fur den aktiven Kalium- und Natrium- Transport durch die Erythrocyten Membran. Helv Physiol Pharmacol Acta 11: 346–354

    CAS  PubMed  Google Scholar 

  33. Skou JC (1957) The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta 23: 394–401

    Article  CAS  PubMed  Google Scholar 

  34. Thomas R, Allen J, Pitts BJR, Schwartz A (1979) Cardenolide analogs. An explanation for the unusual properties of AY 22241. Eur J Pharmacol 53: 227–237

    Article  CAS  PubMed  Google Scholar 

  35. Yoda A (1973) Structure-activity relationships of cardiotonic steroids for the inhibition of sodium- and potassium-dependent adenosine triphosphatase. Dissociation rate constants of various enzyme - cardiac glycoside complexes formed in the presence of magnesium and phosphate. Mol Pharmacol 9: 51–60

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Pharmacodynamie Générale et de Pharmacologie, Université Catholique de Louvain, U.C.L. 7350, Avenue Emmanuel Mounier 73, B-1200, Bruxelles, Belgium

    Prof. Dr. T. Godfraind

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  1. Prof. Dr. T. Godfraind
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Editors and Affiliations

  1. Munich, Germany

    E. Erdmann

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© 1984 Springer-Verlag Berlin Heidelberg

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Godfraind, T. (1984). Subclassification of cardiac glycoside receptors. In: Erdmann, E. (eds) Cardiac Glycoside Receptors and Positive Inotropy. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-642-72376-6_5

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  • DOI: https://doi.org/10.1007/978-3-642-72376-6_5

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-642-72378-0

  • Online ISBN: 978-3-642-72376-6

  • eBook Packages: Springer Book Archive

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