Urocortin (UCN) is a new vasodilator peptide related to corticotrophin-releasing factor family (CRF). The present study was designed to elucidate the effects of UCN in agonist-induced vasoconstriction of rat coronary artery, and its role in the modulation of Ca²⁺ independent phospholipase A2 (iPLA2) and the store operated Ca²⁺ entry (SOCE). We used rat coronary artery to study the effect of UCN on vascular tone, and isolated smooth muscle cells (SMC) loaded with fura-2 to measure intracellular Ca²⁺ changes in presence of UCN.

We observed that SOCE is involved in phenylephrine (PE)-induced coronary vasoconstriction. The inhibition of SOCE channels with 2APB and DES and iPLA2 with BEL produced a suppression of Ca²⁺ influx induced by the emptying of the stores with thapsigargin (TG); and provoked the vasodilatation of coronary artery. In other hand UCN, by the activation of CRF-R2 receptors vasorelaxed PE-induced vasoconstriction independently of the L-type Ca²⁺ channel pathway and in isolated SMC, UCN induced the inhibition of SOCE evoked by TG. Furthermore, we determined that UCN effects on the vasoconstriction and on SOCE were dependent on cAMP/PKA dependent mechanism. In addition, UCN prevented iPLA2 activation and downregulated its mRNA and protein expression. We conclude that UCN produced a vasodilatation by the modulation of iPLA2 and SOCE in rat coronary artery.

Acknowledgements: Ramon y Cajal, FIS (RECAVA, PI050396, PI052106), Consejería de Salud, 0182/2005 and 174/2006