Summary
Proteolytically activated receptors define a new subclass among the G-protein coupled
receptors. Proteinase activated receptor-2 (PAR-2), the second member to be identified
of this growing receptor subclass, can be activated by trypsin and trypsin-like serine
proteases such as mast cell tryptase. PAR-2 is expressed in endothelial cells. Here
we have studied if activation of PAR-2 changes the coagulation properties of cultured
human umbilical vein endothelial cells. We show that activation of PAR-2 induces rapid
and transient formation of tissue factor mRNA with a maximum level 1 hour after receptor
stimulation. The increased mRNA level was accompanied by an increased tissue factor
activity at the endothelial cell surface, shortening coagulation time in a standard
clotting assay. The level of tissue factor activity after PAR-2 activation was comparable
with the effects of thrombin receptor (PAR-1) activation although neither of the two
protease receptors were as strong inducers of tissue factor as tumor necrosis factor-α.