| Catestatin (chromogranin A344-364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart. | |
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MedLine Citation:
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PMID: 18469147 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The catecholamine release-inhibitory catestatin [Cts; human chromogranin (Cg) A(352-372), bovine CgA(344-364)] is a vasoreactive and anti-hypertensive peptide derived from CgA. Using the isolated avascular frog heart as a bioassay, in which the interactions between the endocardial endothelium and the subjacent myocardium can be studied without the confounding effects of the vascular endothelium, we tested the direct cardiotropic effects of bovine Cts and its interaction with beta-adrenergic (isoproterenol, ISO) and endothelin-1 (ET-1) signaling. Cts dose-dependently decreased stroke volume and stroke work, with a threshold concentration of 11 nM, approaching the in vivo level of the peptide. Cts reduced contractility by inhibiting phosphorylation of phospholamban (PLN). Furthermore, the Cts effect was abolished by pretreatment with either nitric oxide synthase (N(G)-monomethyl-l-arginine) or guanylate cyclase (ODQ) inhibitors, or an ET(B) receptor (ET(BR)) antagonist (BQ-788). Cts also noncompetitively inhibited the positive inotropic action of ISO. In addition, Cts inhibited the positive inotropic effect of ET-1, mediated by ET(A) receptors, and did not alter the negative inotropic ET-1 influence mediated by ET(BR). Cts action through ET(BR) was further suggested when, in the presence of BQ-788, Cts failed to inhibit the positive inotropism of both ISO and ET-1 stimulation and PLN phosphorylation. We concluded that the cardiotropic actions of Cts, including the beta-adrenergic and ET-1 antagonistic effects, support a novel role of this peptide as an autocrine-paracrine modulator of cardiac function, particularly when the stressed heart becomes a preferential target of both adrenergic and ET-1 stimuli. |
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Authors:
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Rosa Mazza; Alfonsina Gattuso; Cinzia Mannarino; Bhawanjit K Brar; Sandra Francesca Barbieri; Bruno Tota; Sushil K Mahata |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-05-09 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 295 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-07-15 Completed Date: 2008-08-21 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H113-22 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, University of Calabria, Arcavacata di Rende, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium-Binding Proteins / metabolism Cardiotonic Agents / pharmacology* Cattle Chromogranin A / metabolism* Depression, Chemical Endothelin-1 / metabolism* Enzyme Inhibitors / pharmacology Female Guanylate Cyclase / antagonists & inhibitors, metabolism Humans Isoproterenol / pharmacology* Male Myocardial Contraction / drug effects* Myocardium / metabolism* Nitric Oxide Synthase / antagonists & inhibitors, metabolism Oligopeptides / pharmacology Oxadiazoles / pharmacology Peptide Fragments / metabolism* Phosphorylation Piperidines / pharmacology Quinoxalines / pharmacology Rana esculenta Receptor, Endothelin A / metabolism Receptor, Endothelin B / antagonists & inhibitors, metabolism Signal Transduction / drug effects* Stroke Volume / drug effects omega-N-Methylarginine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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P01 HL-58120/HL/NHLBI NIH HHS; R01 DA-011311/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/BQ 788; 0/Calcium-Binding Proteins; 0/Cardiotonic Agents; 0/Chromogranin A; 0/Endothelin-1; 0/Enzyme Inhibitors; 0/Oligopeptides; 0/Oxadiazoles; 0/Peptide Fragments; 0/Piperidines; 0/Quinoxalines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/chromogranin A (344-364); 0/phospholamban; 17035-90-4/omega-N-Methylarginine; 7683-59-2/Isoproterenol; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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