Advertisement

Apparent equilibrium constant between β-adrenoceptors and a competitive antagonist on a cultured pacemaker cell of mammalian heart

  • Alberto J. Kaumann
  • Rainer Wittmann
Article
  • 15 Downloads

Summary

Heart cells from newborn rats and kittens were cultured. In both species the rate of pacemaker activity of single, cultured cells was increased by low concentrations of catecholamines. The β-adrenoceptor blocker (-)-KL255 antagonized competitively the effects of both, (-)-noradrenaline and (-)-isoprenaline. A mean equilibrium constant of 3.6×10−10 M between (-)-KL255 and β-adrenoceptors of single cells was estimated.

Key words

Drug-β-Adrenoceptor Complex Single Heart Cell 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arunlakshana, O., Schild, H. O.: Some quantitative uses of drug antagonists. Brit. J. Pharmacol.14, 48–58 (1959)Google Scholar
  2. Birnbaumer, L., Pohl, S. L., Kaumann, A. J.: Receptors and acceptors: A necessary distinction in hormone binding studies. Advances in Cyclic Nucleotide Research, Vol. 4; pp. 239–281, edit. by P. Greengard and G. A. Robinson, New York: Raven Press 1974Google Scholar
  3. Blinks, J. R.: Evaluation of the cardiac effects of several beta adrenergic blocking agents. Ann. N. Y. Acad. Sci.139, 673–685 (1967)Google Scholar
  4. Boder, G. B., Johnson, I. S.: Comparative effects of some cardioactive agents on automaticity of cultured heart cells. J. Mol. Cell. Cardiol.4, 453–463 (1972)Google Scholar
  5. Ertel, R. J., Clarke, D. E., Chao, J. C., Francke, F. R.: Autonomic receptor mechanisms in embryonic chick myocardial cell cultures. J. Pharmacol. exp. Ther.178, 73–80 (1971)Google Scholar
  6. Iversen, L. L.: The uptake and storage of noradrenaline in sympathetic nerves. London-Cambridge: University Press 1967Google Scholar
  7. Kaufmann, R., Tritthart, H., Rodenroth, S., Rost, B.: Das mechanische und elektrische Verhalten isolierter embryonaler Herzmuskelzellen in Zellkulturen. Pflügers Arch.311, 25–49 (1969)Google Scholar
  8. Kaumann, A. J.: Adrenergic receptors in heart muscle: Relations among factors influencing the sensitivity of the cat papillary muscle to catecholamines. J. Pharmacol. exp. Ther.173, 383–398 (1970)Google Scholar
  9. Kaumann, A. J.: Potentiation of the effects of isoprenaline and noradrenaline by hydrocortisone in cat heart muscle. Naunyn-Schmiedeberg's Arch. Pharmacol.273, 134–153 (1972)Google Scholar
  10. Kaumann, A. J.: Adrenergic receptors of cardiac muscle. Two different mechanisms of beta-blockers as partial agonists. International Union of Biochemistry, Symposium No. 52, Acta physiol. lat. amer.23, 235–236 (1973)Google Scholar
  11. Kaumann, A. J., Birnbaumer, L.: Adrenergic receptors in heart muscle: Similarity of apparent affinities of beta-blockers for receptors mediating adenyl cyclase activity, inotropic and chronotropic effects of catecholamines. Acta physiol. lat. amer.23, 619–620 (1973)Google Scholar
  12. Kaumann, A. J., Birnbaumer, L.: Characteristics of the adrenergic receptor coupled to myocardial adenylyl cyclase. Stereospecificity and determination of apparent affinity constants for β-blockers. J. biol. Chem.249, in press (1974)Google Scholar
  13. Kaumann, A. J., Blinks, J. R.: Comparative potencies of beta adrenergic blocking agents on isolated heart muscle. Fed. Proc.26, 401 (1967)Google Scholar
  14. Kaumann, A. J., Friedenthal, M., Blinks, J. R.: Análisis de la acción bloqueante de antagonistas beta adrenérgicos en músculo cardíaco aislado. Medicina (B. Aires)30, 596–597 (1970)Google Scholar
  15. Pendleton, R. G., Petta, J. M., Hahn, R. A.: Studies on the myocardial depressant effect of KL255. A beta adrenergic receptor antagonist. Arch. int. Pharmacodyn.187, 75–87 (1970)Google Scholar
  16. Potter, L. T.: Uptake of propranolol by isolated guinea-pig atria. J. Pharmacol. exp. Ther.155, 91–100 (1967)Google Scholar
  17. Sperelakis, N.: In: Electrical phenomena in the heart, p. 32, Ed. W. C. de Mello, New York: Academic Press 1972Google Scholar
  18. Waud, D. R.: Pharmacological receptors. Pharmacol. Rev.20, 49–88 (1968)Google Scholar
  19. Waymouth, Ch.: Rapid proliferation of sublines of NCTC clone 929 (Strain L) mouse cells in a simple chemically defined medium (MB 752/1). J. nat. Cancer Inst.22, 1003–1017 (1959)Google Scholar
  20. West, T. C.: Auricular cellular potentials: Ultramicroelectorode recording of drug effect on nodal and extranodal regions. Fed. Proc.14, 393–394 (1955)Google Scholar
  21. Wollenberger, A.: Rhythmic and arrythmic contractile activity of single myocardial cells culturedin vitro. Circulat. Res. (Suppl. 2)15, 184–201 (1964)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Alberto J. Kaumann
    • 1
  • Rainer Wittmann
    • 1
  1. 1.Lehrstuhl für Klinische PhysiologiePhysiologisches Institut der Universität DüsseldorfDüsseldorf

Personalised recommendations