P041 Topic: Epac1-selective Cyclic-AMP Analog 8-pCPT-2’-O-Me-cAMP Induces Vasodilation On Porcine Coronary Artery In Endothelium-Independent Pathway

Background: Exchange protein directly activated by cyclic AMP (cAMP) 1, Epac1, is a newly discovered cAMP target which acts beyond the classical cAMP effector protein kinase A (PKA). The identification of Epac1 overthrows the concept that cAMP activatez single effector. Epac1 is a guanine nucleotide exchange factor (GEF) probably activates small G-protein Rap1. Epac1 ubiquitously expresses in all tissues and therefore should play important roles in cellular signaling. Appreciation of the potential importance of Epac1 has come with the current development of Epac1-selective-cAMP analogs for discriminating the activation from PKA to Epac1. Among those analogs, 8-pCPT-2'-O-MecAMP (8-pCPT) is the most potent Epac1 activator available (Kd=2.2 μM) with a low affinity to PKA (Kd=200-300 μM). 8-pCPT was revealed to induce aorta and airway relaxation, whereas the underlying mechanism remains unclear. Moreover, to date no comparable data exist on the role of Epac1 in porcine vascular system. Current study aimed to investigate the effect of 8-pCPT in isolated porcine coronary vasodilatation.