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Signal transduction by cGMP in heart

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Summary

Early studies in whole heart indicated that cGMP antagonized the positive inotropic effects of catecholamines and cAMP. However, the regulation of cGMP levels by a variety of agents was not always consistent with their effects on contractility. It is now clear that at least two major cell types in whole heart, cardiac myocytes and vascular smooth muscle cells, differ markedly in their mechanisms of cGMP regulation and response to cGMP. Furthermore, experiments on isolated cardiac myocytes indicate that the mechanism of cGMP action even in this single cell type can be multifaceted. Cyclic GMP inhibits the L-type calcium channel current (ICa), which is the major source of Ca++ entry into heart cells, and which plays a predominant role in the initiation and regulation of cardiac electrical and contractile activities. Patch-clamp measurements of ICa indicate that in isolated frog myocytes cGMP inhibits ICa by stimulation of cAMP phosphodiesterase (cGS-PDE), whereas in purified rat ventricular myocytes, cGMP predominantly inhibits ICa via a mechanism involving cGMP-dependent protein kinase (cGMP-PK). Under certain conditions, cGMP can also inhibit a cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) and thereby produce a stimulatory effect on ICa. Biochemical characterization of the endogenous PDEs and cGMP-PK in purified cardiac myocytes provided further evidence in support of these mechanisms of cGMP action on ICa.

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  1. S. M. Lohmann

    Present address: Medizinische Universitätsklinik, Labor für Klinische Biochemie, Universität Würzburg, Josef-Schneider-Str. 2, 8700, Würzburg, Germany

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  1. Medizinische Universitätsklinik, Labor für Klinische Biochemie, Universität Würzburg, Josef-Schneider-Str. 2, 8700, Würzburg, Germany

    U. Walter

  2. Laboratoire de Physiologie Cellulaire Cardiaque, Institut National de la Santé et de la Recherche Médicale U-241, Université de Paris-Sud, Orsay, France

    R. Fischmeister

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Lohmann, S.M., Fischmeister, R. & Walter, U. Signal transduction by cGMP in heart. Basic Res Cardiol 86, 503–514 (1991). https://doi.org/10.1007/BF02190700

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