Stimulation of proteinase activated receptor-2 causes endothelial cells to promote blood coagulation in vitro.
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-alpha.
Department of Physiology and Neuroscience, Lund University, Sweden. anna-karin.alm@mphy.lu.se
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Alm
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Norström
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Sundelin
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Nystedt
D001777:Blood Coagulation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*
D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin