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The role of cyclic AMP in the positive inotropic effect mediated by β1- and β2-adrenoceptors in isolated human right atrium

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Summary

The time course of the effects of isoprenaline (3 × 10−7 mol/l) on contractile force and on the cyclic AMP level was studied in the electrically driven isolated muscle strip of the human right atrium. Isoprenaline produced a rise in cyclic AMP content (maximum increase after 60 s) preceding the increase in contractile force. The effects of isoprenaline on contractile force and on the intracellular level of cyclic AMP were enhanced in the presence of the phosphodiesterase inhibitor papaverine (10−5 mol/l). On the other hand, the β-adrenoceptor antagonist propranolol (10−7 mol/l) suppressed isoprenaline-induced cyclic AMP increases, but reduced the increase in force of contraction by only 35%. In addition, both the β1-selective antagonist bisoprolol (3 × 10−9 × 10−8 mol/l) and the β2-selective antagonist ICI 118,551 (3 × 10−9 × 10−8 mol/l) inhibited the isoprenaline-induced cyclic AMP increase concentration-dependently; ICI 118,551 produced more pronounced inhibition than bisoprolol. It is concluded that cyclic AMP is involved in the positive inotropic action of isoprenaline evoked by β1- and β2-adrenoceptor stimulation in isolated human right atrium; however, an additional cyclic AMP independent mechanism cannot be ruled out.

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Authors and Affiliations

  1. Biochemical Research Laboratories, Medizinische Klinik and Poliklinik, Division of Renal and Hypertensive Diseases, University of Essen, Hufelandstr. 55, D-4300, Essen, Federal Republic of Germany

    K. Ikezono, M. C. Michel, J. J. Beckeringh & O. E. Brodde

  2. Division of Thoracic and Cardiovascular Surgery, University of Essen, Hufelandstr. 55, D-4300, Essen, Federal Republic of Germany

    H. R. Zerkowski

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  1. K. Ikezono
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  2. M. C. Michel
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  3. H. R. Zerkowski
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  4. J. J. Beckeringh
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  5. O. E. Brodde
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Ikezono, K., Michel, M.C., Zerkowski, H.R. et al. The role of cyclic AMP in the positive inotropic effect mediated by β1- and β2-adrenoceptors in isolated human right atrium. Naunyn-Schmiedeberg's Arch Pharmacol 335, 561–566 (1987). https://doi.org/10.1007/BF00169125

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  • DOI: https://doi.org/10.1007/BF00169125

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