Document Detail


Catestatin (chromogranin A344-364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart.
MedLine Citation:
PMID:  18469147     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rosa Mazza; Alfonsina Gattuso; Cinzia Mannarino; Bhawanjit K Brar; Sandra Francesca Barbieri; Bruno Tota; Sushil K Mahata
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Publication Detail:
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:
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:
Created Date:  2008-07-15     Completed Date:  2008-08-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H113-22     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, University of Calabria, Arcavacata di Rende, Italy.
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MeSH Terms
Descriptor/Qualifier:
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:
P01 HL-58120/HL/NHLBI NIH HHS; R01 DA-011311/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
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

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