title: Urocortin induces positive inotropic effect in rat heart.
abstract: OBJECTIVE
  The aim of this study is to evaluate the positive inotropic effect of urocortin (Ucn) and to characterize its signalling pathways.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratorio de Investigación Cardiovascular, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41013, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Calderón-Sanchez
authors.forename: Carmen
authors.initials: C
authors.lastname: Delgado
authors.forename: Gema
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.forename: Alejandro
authors.initials: A
authors.lastname: Domínguez-Rodríguez
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-Moyano
authors.forename: Ana María
authors.initials: AM
authors.lastname: Gomez
authors.forename: Antonio
authors.initials: A
authors.lastname: Ordóñez
authors.forename: Tarik
authors.initials: T
authors.lastname: Smani
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D055724:Electrophysiological Phenomena; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D054832:Urocortins / Q000494:pharmacology* / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D020662:Guanine Nucleotide Exchange Factors; D047428:Protein Kinase Inhibitors; D054832:Urocortins; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C