title: Nesfatin-1 as a new positive inotrope in the goldfish (Carassius auratus) heart.
abstract: The hypothalamic neuropeptide Nesfatin-1 is present in both mammals and teleosts in which it elicits anorexigenic effects. In mammals, Nesfatin-1 acts on the heart by inducing negative inotropism and lusitropism, and cardioprotection against ischemic damages. We evaluated whether in teleosts, Nesfatin-1 also influences cardiac performance. In the goldfish (Carassius auratus), mature, fully processed Nesfatin-1 was detected in brain, gills, intestine and skeletal muscle, but not in the cardiac ventricle. However, on the isolated and perfused working goldfish heart, exogenous Nesfatin-1 induced a positive inotropic effect, revealed by a dose-dependent increase of stroke volume (SV) and stroke work (SW). Positive inotropism was abolished by inhibition of adenylate cyclase (AC; MDL123330A) and cAMP-dependent kinase (PKA; KT5720), suggesting a cAMP/PKA-mediated pathway. This was confirmed by the increased cAMP concentrations revealed by ELISA on Nesfatin-1-treated hearts. Perfusion with Diltiazem, Thapsigargin and PD98059 showed the involvement of L-type calcium channels, SERCA2a pumps and ERK1/2, respectively. The role of ERK1/2 and phospholamban in Nesfatin-1-induced cardiostimulation was supported by Western blotting analysis. In conclusion, this is the first report showing that in teleosts, Nesfatin-1 potentiates mechanical cardiac performance, strongly supporting the evolutionary importance of the peptide in the control of the cardiac function of vertebrates.
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.ST), 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.ST), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gattuso
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.ST), 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.ST), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cantafio
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Cerra
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: T
authors.initials: T
authors.lastname: Angelone
authors.affiliation: Dept. of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Arcavacata di Rende (CS), Italy. Electronic address: sandra.imbrogno@unical.it.
authors.forename: S
authors.initials: S
authors.lastname: Imbrogno
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006054:Goldfish; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D000080866:Nucleobindins; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000242:Cyclic AMP; D006152:Cyclic GMP; D004268:DNA-Binding Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D000099211:Phospholamban
keywords: Cardiac performance; Inotropism; Nesfatin-1; Signal transduction; cAMP