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New Perspectives in cAMP-Signaling Modulation

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Abstract

Cyclic adenosine 3′,5′-monophosphate (cAMP) mediates the biological effects of various hormones and neurotransmitters. Stimulation of cardiac β-adrenergic receptors (β-AR) via catecholamines leads to activation of adenylyl cyclases and increases cAMP production to enhance myocardial function. Because many other receptors signaling through cAMP generation exist in cardiac myocytes, a central question is how different hormones induce distinct cellular responses through the same second messenger. A large body of evidence suggests that the localization and compartmentalization of β-AR/cAMP signaling affects the net outcome of biological functions. Spatiotemporal dynamics of cAMP action is achieved by various proteins, including protein kinase A (PKA), phosphodiesterases, and scaffolding proteins such as A-kinase–anchoring proteins. In addition, the discovery of the cAMP target Epac (exchange proteins directly activated by cAMP), which functions in a PKA-independent manner, represents a novel mechanism for governing cAMP-signaling specificity. Aberrant cAMP signaling through dysregulation of β-AR/cAMP compartmentalization may contribute to cardiac remodeling and heart failure.

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Acknowledgements

We thank Drs. Jeanne Mialet-Perez and Bertrand Crozatier for their critical reading of the manuscript. The work of Dr. Frank Lezoualc’h mentioned herein was supported by grants from Agence Nationale de la Recherche («HyperEpac» Genopath09) to Région Midi-Pyrénées. Drs. Magali Breckler, Magali Berthouze, and Anne-Coline Laurent were recipients of grants from Région île-de-France (CODIM), Fondation Lefoulon Delalande, and Groupe de Réflexion sur la Recherche Cardiovasculaire (G.R.R.C)/Fédération Française de Cardiologie (F. F. C).

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. INSERM, UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, 1 Avenue Jean Poulhès, BP 84225, 31342, Toulouse Cedex 4, France

    Magali Berthouze & Frank Lezoualc’h

  2. Université de Toulouse III, Paul Sabatier, Toulouse, 31342, France

    Magali Berthouze & Frank Lezoualc’h

  3. INSERM, UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, 31342, France

    Anne-Coline Laurent & Magali Breckler

  4. Université de Toulouse III, Paul Sabatier, Toulouse, 31342, France

    Anne-Coline Laurent & Magali Breckler

  5. Université Paris-Sud 11, Orsay, France

    Anne-Coline Laurent & Magali Breckler

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  1. Magali Berthouze
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  2. Anne-Coline Laurent
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  3. Magali Breckler
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  4. Frank Lezoualc’h
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Correspondence to Frank Lezoualc’h.

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Berthouze, M., Laurent, AC., Breckler, M. et al. New Perspectives in cAMP-Signaling Modulation. Curr Heart Fail Rep 8, 159–167 (2011). https://doi.org/10.1007/s11897-011-0062-8

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