Stimulation at proteinase activated receptor-2 causes endothelial cells topromote blood coagulation in vitro

Proteolytically activated receptors define a new subclass among the G-prote in coupled receptors. Proteinase activated receptor-2 (PAR-2), the second m ember to be identified of this growing receptor subclass, can be activated by trypsin and trypsin-like serine proteases such as mast cell tryptase. PA R-2 is expressed in endothelial cells. Here we have studied if activation o f PAR-2 changes the coagulation properties of cultured human umbilical vein endothelial cells. We show that activation of PAR-2 induces. rapid and tra nsient formation of tissue factor mRNA with a maximum level 1 hour after re ceptor stimulation. The increased mRNA level was accompanied by an increase d tissue factor activity at the endothelial cell surface, shortening coagul ation time in a standard clotting assay. The level of tissue factor activit y after PAR-2 activation was comparable with the effects of thrombin recept or (PAR-1) activation although neither of the two protease receptors were a s strong inducers of tissue. factor as tumor necrosis factor-alpha.