HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.08-110239v1 22/11/3992    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cerra, M. C. Articles by Alloatti, G. Search for Related Content PubMed PubMed Citation Articles by Cerra, M. C. Articles by Alloatti, G.

The homologous rat chromogranin A1–64 (rCGA1–64) modulates myocardial and coronary function in rat heart to counteract adrenergic stimulation indirectly via endothelium-derived nitric oxide

M. C. Cerra^*,, M. P. Gallo, T. Angelone^*, A. M. Quintieri, E. Pulerà, E. Filice, B. Guérold, P. Shooshtarizadeh, R. Levi, R. Ramella, A. Brero, O. Boero, M. H. Metz-Boutigue, B. Tota^*,1 and G. Alloatti^,1

^* Department of Cell Biology and

Department of Pharmaco-Biology, University of Calabria, Calabria, Italy;

Department of Animal and Human Biology, University of Turin, Turin, Italy; and

Unity INSERM 575, Physiopathology of Nervous System, University "Louis Pasteur," Strasbourg, France

¹ Correspondence: B.T., Department of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Calabria, Italy. E-mail: tota{at}unical.it; A.G., Department of Animal and Human Biology, University of Turin (TO), Italy. E-mail: giuseppe.alloatti{at}unito.it

Chromogranin A (CGA), produced by human and rat myocardium, generates several biologically active peptides processed at specific proteolytic cleavage sites. A highly conserved cleavage N-terminal site is the bond 64–65 that reproduces the native rat CGA sequence (rCGA1–64), corresponding to human N-terminal CGA-derived vasostatin-1. rCGA1–64 cardiotropic activity has been explored in rat cardiac preparations. In Langendorff perfused rat heart, rCGA1–64 (from 33 nM) induced negative inotropism and lusitropism as well as coronary dilation, counteracting isoproterenol (Iso) - and endothelin-1 (ET-1) -induced positive inotropic effects and ET-1-dependent coronary constriction. rCGA1–64 also depressed basal and Iso-induced contractility on rat papillary muscles, without affecting calcium transients on isolated ventricular cells. Structure-function analysis using three modified peptides on both rat heart and papillary muscles revealed the disulfide bridge requirement for the cardiotropic action. A decline in Iso intrinsic activity in the presence of the peptides indicates a noncompetitive antagonistic action. Experiments on rat isolated cardiomyocytes and bovine aortic endothelial cells indicate that the negative inotropism observed in rat papillary muscle is probably due to an endothelial phosphatidylinositol 3-kinase-dependent nitric oxide release, rather than to a direct action on cardiomyocytes. Taken together, our data strongly suggest that in the rat heart the homologous rCGA1–64 fragment exerts an autocrine/paracrine modulation of myocardial and coronary performance acting as stabilizer against intense excitatory stimuli.—Cerra, M. C., Gallo, M. P., Angelone, T., Quintieri, A. M., Pulerà, E., Filice, E., Guérold, B., Shooshtarizadeh, P., Levi, R., Ramella, R., Brero, A., Boero, O., Metz-Boutigue, M. H., Tota, B., Alloatti, G. The homologous rat chromogranin A1–64 (rCGA1–64) modulates myocardial and coronary function in rat heart to counteract adrenergic stimulation indirectly via endothelium-derived nitric oxide.

Key Words: endocrine heart • peptide hormones • endothelial cells • stress response

This article has been cited by other articles:

				R. Granata, L. Trovato, M. P. Gallo, S. Destefanis, F. Settanni, F. Scarlatti, A. Brero, R. Ramella, M. Volante, J. Isgaard, et al. Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart Cardiovasc Res, July 15, 2009; 83(2): 303 - 312. [Abstract] [Full Text] [PDF]