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Urocortin induces positive inotropic effect in rat heart.

Authors: Calderon-Sanchez, E  Delgado, C  Ruiz-Hurtado, G  Dominguez-Rodriguez, A  Cachofeiro, V  Rodriguez-Moyano, M  Gomez, AM  Ordonez, A  Smani, T 
Citation: Calderon-Sanchez E, etal., Cardiovasc Res. 2009 Sep 1;83(4):717-25. Epub 2009 May 21.
Pubmed: (View Article at PubMed) PMID:19460778
DOI: Full-text: DOI:10.1093/cvr/cvp161

AIMS: The aim of this study is to evaluate the positive inotropic effect of urocortin (Ucn) and to characterize its signalling pathways. METHODS AND RESULTS: Contractility was measured in ex vivo Langendorff-perfused hearts isolated from Wistar rats. Isolated ventricular cardiomyocytes were used to analyse intracellular calcium ([Ca(2+)](i)) transients evoked by electrical stimulation and L-type Ca(2+) current by confocal microscopy and whole-cell patch-clamping, respectively. The application of Ucn to perfused hearts induced progressive, sustained, and potent inotropic and lusitropic effects that were dose-dependent with an EC(50) of approximately 8 nM. Ucn effects were independent of protein kinase A (PKA) activation but were significantly reduced by protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors and by brefeldin A, an antagonist of guanine nucleotide exchange factor, suggested to be an inhibitor of exchange protein activated by cAMP (Epac). These whole-organ effects were correlated with the inotropic effects observed in isolated cells: Ucn increased I(CaL) density, [Ca(2+)](i) transients, cell shortening and Ca(2+) content of sarcoplasmic reticulum. CONCLUSION: Our results show that Ucn evokes potent positive inotropic and lusitropic effects mediated, at least in part, by an increase in I(CaL) and [Ca(2+)](i) transient amplitude. These effects may involve the activation of Epac, PKC, and MAPK signalling pathways.


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CRRD Object Information
CRRD ID: 5508168
Created: 2011-10-05
Species: All species
Last Modified: 2011-10-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.