title: The Chromogranin A-derived sympathomimetic serpinin depresses myocardial performance in teleost and amphibian hearts.
abstract: Chromogranin A (CgA) is an acidic protein co-stored with catecholamines, hormones and neuropeptides in the secretory granules of endocrine, neuronal and other cell types (including cardiomyocytes). Proteolytic cleavage in the C terminus of CgA generates a 2.9kDa peptide named serpinin (Serp; Ala26Leu) that can be modified at its N terminus to form a pyroglutamate residue (pGlu-Serp). In the rat heart, both peptides increase contractility and relaxation through a β-adrenergic-like action mechanism. Accordingly, Serp and pGlu-Serp were proposed as novel myocardial sympatho-adrenergic modulators in mammals. On a comparative basis, here we report the actions of Serp and pGlu-Serp on myocardial contractility in three poikilotherm vertebrate species: the eel (Anguilla anguilla), the goldfish (Carassius auratus) and the frog (Rana esculenta). Using isolated working heart preparations, we show that pGlu-Serp reduces stroke volume in all species tested, while Serp reduces contractility in the frog heart, but is uneffective in eel and goldfish hearts. In the goldfish and frog hearts, pGlu-Serp activates the Nitric Oxide/cGMP pathway involving Endothelin-1 B receptors (frog) and β3adrenergic receptors (goldfish). pGlu-Serp-treated hearts from goldfish and frog show increased cGMP content. Moreover, the exposure of the frog heart to pGlu-Serp is accompanied by an increased expression of activated eNOS and Akt. In conclusion, this first report showing that pGlu-Serp inhibits mechanical cardiac performance in teleost and amphibians supports an evolutionary role of the CgA system, and particularly its serpinin component, in the sympatho-adrenergic control of the vertebrate heart.
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy. Electronic address: sandra.imbrogno@unical.it.
authors.forename: S
authors.initials: S
authors.lastname: Imbrogno
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mazza
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pugliese
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: M
authors.initials: M
authors.lastname: Filice
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: T
authors.initials: T
authors.lastname: Angelone
authors.affiliation: Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Y P
authors.initials: YP
authors.lastname: Loh
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: B
authors.initials: B
authors.lastname: Tota
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.S.T.), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Cerra
mesh_terms: D000663:Amphibians / Q000378:metabolism*; D000818:Animals; D053379:Chromogranin A / Q000235:genetics*; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D015398:Signal Transduction; D013566:Sympathomimetics / Q000378:metabolism*
chemical_list: D053379:Chromogranin A; D010446:Peptide Fragments; D013566:Sympathomimetics
keywords: Cardiac performance; ET(B) receptors; Negative inotropism; Sympatho-adrenergic signaling; cGMP; β3-Adrenoceptors