Urocortin II induces nitric oxide production through cAMP and Ca 2+ related pathways in endothelial cells

Elena Grossini, Claudio Molinari, David A.S.G. Mary, Francesca Uberti, Flavio Ribichini, Philippe Primo Caimmi, Giovanni Vacca

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Urocortin II has previously been shown in anesthetized pigs to increase coronary blood flow through activation of the endothelial nitric oxide synthase (eNOS) pathway and involvement of the subtype 2 of corticotropin releasing factor receptors (CRFR2). However, little information has been available regarding the intracellular signalling through these receptors and leading to the release of nitric oxide (NO). Aim: The present study was therefore planned to determine the mechanism involved in such signalling. Methods: In porcine aortic endothelial cells (PAE) the effects of urocortin II on NO production and ERK, Akt, p38 and eNOS phosphorylation were examined in absence or presence of the adenylyl cyclase agonist forskolin and antagonist 2′5′ dideoxyadenosine, the Ca 2+ ionophore A23187, the Ca 2+ -calmodulin-kinase inhibitor KN93, the CRFR2 blocker astressin 2B and of the protein kinases specific inhibitors UO126, wortmannin and SB203580. Results: Urocortin II caused a significant increase of NO production, which was amplified by forskolin and A23187 (P <0.05). All effects of urocortin II were abolished by l-NAME, 2′5′ dideoxyadenosine, KN93, astressin 2B and by pre-treatment of cells with UO126, wortmannin and SB203580. Western Blot analysis confirmed the involvement of ERK, Akt and p38 in the eNOS activation. Conclusion: In PAE urocortin II interaction with CRFR2 caused a cAMP-dependent and Ca 2+ -related phoshorylation of ERK, Akt and p38 leading to eNOS activation.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalCellular Physiology and Biochemistry
Volume23
Issue number1-3
DOIs
Publication statusPublished - 2009

Keywords

  • Endothelial cells
  • Nitric Oxide
  • Urocortin II

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