Figure 1: Permeability change by induced secretion of Ang-2: opposing effects depending on different secretary agonists. A. Although epinephrine induces WBP exocytosis, thus Ang-2 secretion, it rather decreases EC permeability by a direct effect on Rac1 activation mediated by cAMPPKA pathway. B. Thrombin induces increased EC permeability by PLC-Ca2+ mediated Ang-2 exocytosis which results in RhoA activation. C. Thrombin, in the presence of protein C in EPCR, induces decreased EC permeability mediated by Gi protein-PI3K-Akt and/or transactivation of S1P1 and by increasing expression of Ang-1- Tie-2, subsequently resulting in Rac1 activation. Gs, Gq, Gi, G protein –coupled receptors; AC, adenylyl cyclase; PKA, protein kinase A; PLC, phospholipase C; PIP2, phosphatidylinositol biphosphate; IP3, inositol (1,4,5) triphosphate; CaM, calmodulin; EPCR, endothelial protein C receptor; S1P1, sphingosine 1-phosphate receptor; PI3k, phosphatidylinositol 3-kinase; Akt [74,141].