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

被引:43
作者
Cerra, M. C. [1 ,2 ]
Gallo, M. P. [3 ]
Angelone, T. [1 ]
Quintieri, A. M. [2 ]
Pulera, E. [2 ]
Filice, E. [2 ]
Guerold, B. [4 ]
Shooshtarizadeh, P. [4 ]
Levi, R. [3 ]
Ramella, R. [3 ]
Brero, A. [3 ]
Boero, O. [3 ]
Metz-Boutigue, M. H. [4 ]
Tota, B. [1 ]
Alloatti, G. [3 ]
机构
[1] Univ Calabria, Dept Cell Biol, I-87030 Calabria, Italy
[2] Univ Calabria, Dept Pharmacobiol, I-87030 Calabria, Italy
[3] Univ Turin, Dept Anim & Human Biol, Turin, Italy
[4] Univ Strasbourg, Unity INSERM 575, Strasbourg, France
关键词
endocrine heart; peptide hormones; endothelial cells; stress response;
D O I
10.1096/fj.08-110239
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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., Pulera, E., Filice, E., Guerold, 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. FASEB J. 22, 3992 - 4004 (2008)
引用
收藏
页码:3992 / 4004
页数:13
相关论文
共 53 条
[1]   VASOSTATINS, COMPRISING THE N-TERMINAL DOMAIN OF CHROMOGRANIN-A, SUPPRESS TENSION IN ISOLATED HUMAN BLOOD-VESSEL SEGMENTS [J].
AARDAL, S ;
HELLE, KB ;
ELSAYED, S ;
REED, RK ;
SERCKHANSSEN, G .
JOURNAL OF NEUROENDOCRINOLOGY, 1993, 5 (04) :405-412
[2]   G protein-mediated inhibitory effect of a nitric oxide donor on the L-type Ca2+ current in rat ventricular myocytes [J].
Abi-Gerges, N ;
Fischmeister, R ;
Méry, PF .
JOURNAL OF PHYSIOLOGY-LONDON, 2001, 531 (01) :117-130
[3]   The emerging cardioinhibitory role of the hippocampal cholinergic neurostimulating peptide [J].
Angelone, Tommaso ;
Goumon, Yannick ;
Cerra, Maria Carmela ;
Metz-Boutigue, Marie-Helene ;
Aunis, Dominique ;
Tota, Bruno .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 318 (01) :336-344
[4]  
Atherton E, 1989, SOLID PHASE PEPTIDE
[5]   EFFECTS OF ENDOTHELIN-1 ON THE RAT ISOLATED HEART [J].
BAYDOUN, AR ;
PEERS, SH ;
CIRINO, G ;
WOODWARD, B .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1989, 13 :S193-S196
[6]   Prohormone and proneuropeptide processing - Recent progress and future challenges [J].
Beinfeld, MC .
ENDOCRINE, 1998, 8 (01) :1-5
[7]   N-terminal chromogranin-derived peptides as dilators of bovine coronary resistance arteries [J].
Brekke, JF ;
Osol, GJ ;
Helle, KB .
REGULATORY PEPTIDES, 2002, 105 (02) :93-100
[8]  
BRUNNER F, 2006, PHARMACOL THERAPEUT, V26, P364
[9]   RELAXATION AND DIASTOLE OF THE HEART [J].
BRUTSAERT, DL ;
SYS, SU .
PHYSIOLOGICAL REVIEWS, 1989, 69 (04) :1228-1315
[10]   Human recombinant chromogranin A-derived vasostatin-1 mimics preconditioning via an adenosine/nitric oxide signaling mechanism [J].
Cappello, Sandra ;
Angelone, Tommaso ;
Tota, Bruno ;
Pagliaro, Pasquale ;
Penna, Claudia ;
Rastaldo, Raffaella ;
Corti, Angelo ;
Losano, Gianni ;
Cerra, Maria Carmela .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2007, 293 (01) :H719-H727