title: Peptides from the N-terminal domain of chromogranin A (vasostatins) exert negative inotropic effects in the isolated frog heart.
abstract: The negative inotropic effects of synthetic peptides derived from the N-terminus of chromogranin A (CgA) were studied in an avascular model of the vertebrate myocardium, the isolated working frog heart (Rana esculenta). The peptides were frog and bovine CgA(4-16) and CgA(47-66), and bovine CgA(1-40) with (CgA(1-40SS)) and without an intact disulfide bridge (CgA(1-40SH)). Under basal cardiac conditions, four of the peptides caused a concentration-dependent negative inotropism that was comparable to the negative inotropy reported for human recombinant vasostatin I (CgA(1-78)) and bovine CgA(7-57). By comparison of the structural characteristics of the bovine and frog sequences with their minimally effective concentrations ranging from 68 to 125 nM of peptide, the results were consistent with the natural structure (CgA(17-38SS)) being essential for the negative inotropism. In addition, the partial sequences of the frog and bovine vasostatin I were effective in counteracting the characteristic positive inotropism exerted by isoproterenol (1 nM) at minimally effective concentrations ranging from 45 to 272 nM. Taken together, these results extend the first evidence for a cardiosuppressive role of the N-terminal domain of chromogranin A known for its co-storage with catecholamines in the sympathoadrenal system of vertebrates.
authors.affiliation: Department of Cell Biology, University of Calabria, 87030 Arcavata di Rende CS, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tota
authors.forename: Rosa
authors.initials: R
authors.lastname: Mazza
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
authors.forename: Gerard
authors.initials: G
authors.lastname: Nullans
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Karen B
authors.initials: KB
authors.lastname: Helle
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry*; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011893:Rana esculenta
chemical_list: D000318:Adrenergic beta-Agonists; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; D007545:Isoproterenol