The regulatory mechanisms of vascular endothelial barrier function are complicated. Inflammatory mediators, such as alpha-thrombin, activate phospholipases to mediate generation of IP3 and other second messengers through receptor-coupled G protein. Protein kinase C and myosin light chain kinase are then activated, leading to phosphorylation of myosin light chains, rearrangement of F-actin skeleton, interendothelial cell gap formation and increased endothelial permeability.