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. 1972 Nov;46(3):488–497. doi: 10.1111/j.1476-5381.1972.tb08146.x

The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

T Godfraind, M Lesne
PMCID: PMC1666540  PMID: 4656610

Abstract

1. The uptake of 3H-digitoxin, 3H-ouabain and 3H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect.

2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished.

3. The uptake of inactive doses of dihydro-ouabain was only by a non-saturable mechanism.

4. The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake.

5. The uptake was reduced at 4° C to the clearance of the non-saturable site.

6. ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site.

7. It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker P. F., Willis J. S. Potassium ions and the binding of cardiac glycosides to mammalian cells. Nature. 1970 May 9;226(5245):521–523. doi: 10.1038/226521a0. [DOI] [PubMed] [Google Scholar]
  2. DUNHAM E. T., GLYNN I. M. Adenosinetriphosphatase activity and the active movements of alkali metal ions. J Physiol. 1961 Apr;156:274–293. doi: 10.1113/jphysiol.1961.sp006675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DUTTA S., MARKS B. H., SMITH C. R. DISTRIBUTION AND EXCRETION OF OUABAIN-H3 AND DIHYDRO-OUABAIN-H3 IN RATS AND SHEEP. J Pharmacol Exp Ther. 1963 Nov;142:223–230. [PubMed] [Google Scholar]
  4. Dutta S., Goswami S., Datta D. K., Lindower J. O., Marks B. H. The uptake and binding of six radiolabeled cardiac glycosides by guinea-pig hearts and by isolated sarcoplasmic reticulum. J Pharmacol Exp Ther. 1968 Nov;164(1):10–21. [PubMed] [Google Scholar]
  5. Dutta S., Goswami S., Lindower J. O., Marks B. H. Subcellular distribution of digoxin-H3 in isolated guinea-pig and rat hearts. J Pharmacol Exp Ther. 1968 Feb;159(2):324–334. [PubMed] [Google Scholar]
  6. GLYNN I. M. THE ACTION OF CARDIAC GLYCOSIDES ON ION MOVEMENTS. Pharmacol Rev. 1964 Dec;16:381–407. [PubMed] [Google Scholar]
  7. Gillis J. M. Les mouvements de l'eau dans le muscle strié isolé soumis à des tétanisations répétées. Arch Int Physiol Biochim. 1964 Jan;72(1):154–170. doi: 10.3109/13813456409105259. [DOI] [PubMed] [Google Scholar]
  8. Godfraind T. A pharmacological approach to the mode of digitalis action. Verh K Vlaam Acad Geneeskd Belg. 1969;31(5):315–354. [PubMed] [Google Scholar]
  9. Godfraind T., Godfraind-de Becker A. The action of ouabain on the response of the isolated guinea-pig auricles to catecholamines in relation with its chronotropic and inotropic effects. Arch Int Pharmacodyn Ther. 1965 Dec;158(2):453–465. [PubMed] [Google Scholar]
  10. Godfraind T., Lesne M. Estimation of digitoxin uptake by isolated cardiac and smooth muscle preparations. Arch Int Pharmacodyn Ther. 1967 Mar;166(1):195–199. [PubMed] [Google Scholar]
  11. Godfraind T., Lesne M. Les récepteurs digitaliques du muscle cardiaque. Arch Int Pharmacodyn Ther. 1971 Apr;190(2):402–403. [PubMed] [Google Scholar]
  12. Godfraind T., Lesne M. Specific and non-specific uptake of cardiac glycosides. Naunyn Schmiedebergs Arch Pharmakol. 1970;266(4):334–335. doi: 10.1007/BF00997973. [DOI] [PubMed] [Google Scholar]
  13. Godfraind T., Lesne M. The uptake of cardiac glycosides by intestinal smooth muscle of the guinea-pig in relation to digitalis receptors. Br J Pharmacol. 1970 Feb;38(2):345–352. doi: 10.1111/j.1476-5381.1970.tb08522.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Godfriand T., Lesne M. Relative potency of digitoxin and digoxin in relation with their binding to isolated cardiac and smooth muscles. Arch Int Pharmacodyn Ther. 1968 Jan;171(1):228–230. [PubMed] [Google Scholar]
  15. Kuschinsky K., Lahrtz H., Lüllmann H., van Zwieten P. A. Accumulation and release of 3H-digoxin by guinea-pig heart muscle. Br J Pharmacol Chemother. 1967 Jun;30(2):317–328. doi: 10.1111/j.1476-5381.1967.tb02138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuschinsky K., Lüllmann H., van Zwieten P. A. A comparison of the accumulation and release of 3H-ouabain and 3H-digitoxin by guinea-pig heart muscle. Br J Pharmacol Chemother. 1968 Mar;32(3):598–608. doi: 10.1111/j.1476-5381.1968.tb00460.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee K. S., Klaus W. The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol Rev. 1971 Sep;23(3):193–261. [PubMed] [Google Scholar]
  18. Lukas D. S. Some aspects of the distribution and disposition of digitoxin in man. Ann N Y Acad Sci. 1971 Jul 6;179:338–361. doi: 10.1111/j.1749-6632.1971.tb46912.x. [DOI] [PubMed] [Google Scholar]
  19. Lüllmann H., van Zwieten P. A. The kinetic behaviour of cardiac glycosides in vivo, measured by isotope techniques. J Pharm Pharmacol. 1969 Jan;21(1):1–8. doi: 10.1111/j.2042-7158.1969.tb08121.x. [DOI] [PubMed] [Google Scholar]
  20. Potter L. T. Uptake of propranolol by isolated guinea-pig atria. J Pharmacol Exp Ther. 1967 Jan;155(1):91–100. [PubMed] [Google Scholar]
  21. REPKE K., PORTIUS H. J. UBER DIE IDENTITAET DER IONENPUMPEN-ATPASE IN DER ZELLMEMBRAN DES HERZMUSKELS MIT EINEM DIGITALIS-REZEPTORENZYM. Experientia. 1963 Sep 15;19:452–458. doi: 10.1007/BF02150643. [DOI] [PubMed] [Google Scholar]
  22. Reiter M. Die Wertbestimmung inotrop wirkender Arzneimittel am isolierten Papillarmuskel. Arzneimittelforschung. 1967 Oct;17(10):1249–1253. [PubMed] [Google Scholar]
  23. Schwartz A., Allen J. C., Harigaya S. Possible involvement of cardiac Na+, K+-adenosine triphosphatase in the mechanism of action of cardiac glycosides. J Pharmacol Exp Ther. 1969 Jul;168(1):31–41. [PubMed] [Google Scholar]
  24. Schwartz A., Matsui H., Laughter A. H. Tritiated digoxin binding to (Na+ + K+)-activated adenosine triphosphatase: possible allosteric site. Science. 1968 Apr 19;160(3825):323–325. doi: 10.1126/science.160.3825.323. [DOI] [PubMed] [Google Scholar]

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