The catecholamine release-inhibitory peptide catestatin (chromogranin A344-363) modulates myocardial function in fish.
Catestatin (CST), the 21-amino acid, cationic and hydrophobic peptide proteolytically derived from the ubiquitous chromogranin A (CgA), is an endogenous inhibitor of catecholamine release, a potent vasodilator in vivo and an anti-hypertensive agent in mammals, including humans. Recently, we discovered that CST also functions as an important negative modulator of heart performance in frog and rat. To gain an evolutionary perspective on CST cardiotropism in fish, we analysed the influence of bovine CST (CgA₃₄₄₋₃₆₄) on the eel heart, as well as the eventual species-specific mechanisms of its myocardial action. Experiments were carried out on fresh-water eels (Anguilla anguilla L.) using an electrically paced isolated working heart preparation. Stroke volume and stroke work were used as measures of ventricular performance. Under basal conditions, CST (from 11 nmol l⁻¹ to 165 nmol l⁻¹) caused a concentration-dependent negative inotropism, which was abolished by inhibitors of either β₁/β₂ (propranolol) or β₃ (SR₅₉₂₃₀) adrenergic receptors, or by G(i/o) protein (PTx) or nitric oxide synthase (L-NMMA), or guanylate cyclase (ODQ) blockers. This suggests a β-adrenergic receptor-G(i/o) protein-NO-cGMP-dependent mechanism. By contrast, the CST-induced cardio-suppression was not influenced by atropine, unspecific muscarinic antagonist, thus excluding cholinergic receptor involvement. CST also counteracted the adrenergic (isoproterenol)-mediated positive inotropism. Under increased preload (i.e. Frank-Starling response) conditions, CST induced a significant increase of the Frank-Starling response, which was blocked by L-NMMA and thapsigargin, but independent from guanylate cyclase. In conclusion, this is the first report in fish that CST modulates myocardial performance under basal, as well as under increased preload, conditions and counteracts the adrenergic-mediated positive inotropism, which strikingly supports the evolutionary significance and establishes the cardioactive role of this peptide.
Department of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy.
Sandra
S
Imbrogno
Filippo
F
Garofalo
Maria Carmela
MC
Cerra
Sushil K
SK
Mahata
Bruno
B
Tota
D000595:Amino Acid Sequence; D000811:Anguilla / Q000502:physiology*; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015153:Blotting, Western; D002417:Cattle; D053379:Chromogranin A / Q000737:chemistry / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006334:Heart Function Tests; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects
D053379:Chromogranin A; D010446:Peptide Fragments; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; C109084:chromogranin A (344-364); D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D006152:Cyclic GMP