TRYPSIN INDUCED VON-WILLEBRAND-FACTOR RELEASE FROM HUMAN ENDOTHELIAL-CELLS IS MEDIATED BY PAR-2 ACTIVATION

Nystedt and co-workers cloned in 1994 a second protease activatable re ceptor (PAR-2) that could be activated by trypsin but not by thrombin (1). In this study, we investigated whether trypsin induced stimulatio n of endothelial cells is linked to PAR-2 activation. We have found by mRNA analysis that endothelial cells of venous and arterial origin ex press both protease activatable receptors. The functional thrombin rec eptor and the protease activated receptor-2 (PAR-2) mediate apparently the same effects in human vascular endothelial cells. Both, the activ ation of the thrombin receptor with thrombin or SFLLRN and the activat ion of the PAR-2 with trypsin or SLIGRL, induced intracellular calcium mobilisation and a subsequent release of von Willebrand factor (vWf) from Weibel-Palade bodies. As a consequence, it can be concluded that endothelial cells have two different receptors mediating the same cell ular responses after activation. Copyright (C) 1996 Elsevier Science L td