Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts |
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| Authors: | Gaia Calamera Lise Romn Moltzau Finn Olav Levy Kjetil Wessel Andressen |
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| Affiliation: | Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057 Blindern, 0316 Oslo, Norway; (G.C.); (L.R.M.); (F.O.L.) |
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| Abstract: | Cardiac contractility is regulated by several neural, hormonal, paracrine, and autocrine factors. Amongst these, signaling through β-adrenergic and serotonin receptors generates the second messenger cyclic AMP (cAMP), whereas activation of natriuretic peptide receptors and soluble guanylyl cyclases generates cyclic GMP (cGMP). Both cyclic nucleotides regulate cardiac contractility through several mechanisms. Phosphodiesterases (PDEs) are enzymes that degrade cAMP and cGMP and therefore determine the dynamics of their downstream effects. In addition, the intracellular localization of the different PDEs may contribute to regulation of compartmented signaling of cAMP and cGMP. In this review, we will focus on the role of PDEs in regulating contractility and evaluate changes in heart failure. |
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| Keywords: | cardiomyocyte inotropic response lusitropic response beta-adrenergic receptor GC-A GC-B ANP BNP CNP 5-HT4 |
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