Chromogranin A (CGA), produced byhuman and rat myocardium, generates several biologicallyactive peptides processed at specific proteolyticcleavage sites. A highly conserved cleavage N-terminalsite is the bond 64–65 that reproduces the native ratCGA sequence (rCGA1–64), corresponding to humanN-terminal CGA-derived vasostatin-1. rCGA1–64 cardiotropicactivity has been explored in rat cardiacpreparations. In Langendorff perfused rat heart,rCGA1–64 (from 33 nM) induced negative inotropismand lusitropism as well as coronary dilation, counteractingisoproterenol (Iso) - and endothelin-1 (ET-1)-induced positive inotropic effects and ET-1-dependentcoronary constriction. rCGA1–64 also depressed basaland Iso-induced contractility on rat papillary muscles,without affecting calcium transients on isolated ventricularcells. Structure-function analysis using three modifiedpeptides on both rat heart and papillary musclesrevealed the disulfide bridge requirement for the cardiotropicaction. A decline in Iso intrinsic activity in thepresence of the peptides indicates a noncompetitiveantagonistic action. Experiments on rat isolated cardiomyocytesand bovine aortic endothelial cells indicatethat the negative inotropism observed in rat papillarymuscle is probably due to an endothelial phosphatidylinositol3-kinase-dependent nitric oxide release, ratherthan to a direct action on cardiomyocytes. Taken together,our data strongly suggest that in the rat heartthe homologous rCGA1–64 fragment exerts an autocrine/paracrine modulation of myocardial and coronaryperformance acting as stabilizer against intenseexcitatory stimuli.—

The homologous rat Chromogranin A1-64 (rCGA1-64) modulates myocardial and coronary function in the rat heart counteracting the adrenergic modulation through endothelium-derived Nitric Oxide mechanisms

CERRA, Maria Carmela;ANGELONE, Tommaso;
2008

Abstract

Chromogranin A (CGA), produced byhuman and rat myocardium, generates several biologicallyactive peptides processed at specific proteolyticcleavage sites. A highly conserved cleavage N-terminalsite is the bond 64–65 that reproduces the native ratCGA sequence (rCGA1–64), corresponding to humanN-terminal CGA-derived vasostatin-1. rCGA1–64 cardiotropicactivity has been explored in rat cardiacpreparations. In Langendorff perfused rat heart,rCGA1–64 (from 33 nM) induced negative inotropismand lusitropism as well as coronary dilation, counteractingisoproterenol (Iso) - and endothelin-1 (ET-1)-induced positive inotropic effects and ET-1-dependentcoronary constriction. rCGA1–64 also depressed basaland Iso-induced contractility on rat papillary muscles,without affecting calcium transients on isolated ventricularcells. Structure-function analysis using three modifiedpeptides on both rat heart and papillary musclesrevealed the disulfide bridge requirement for the cardiotropicaction. A decline in Iso intrinsic activity in thepresence of the peptides indicates a noncompetitiveantagonistic action. Experiments on rat isolated cardiomyocytesand bovine aortic endothelial cells indicatethat the negative inotropism observed in rat papillarymuscle is probably due to an endothelial phosphatidylinositol3-kinase-dependent nitric oxide release, ratherthan to a direct action on cardiomyocytes. Taken together,our data strongly suggest that in the rat heartthe homologous rCGA1–64 fragment exerts an autocrine/paracrine modulation of myocardial and coronaryperformance acting as stabilizer against intenseexcitatory stimuli.—
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/154173
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 43
  • ???jsp.display-item.citation.isi??? 41
social impact