Evidence for proteinase-activated receptor-2 (PAR-2)-mediated mitogenesis in coronary artery smooth muscle cells

1 This study investigates, whether in addition to the thrombin receptor (PA R-1), the proteinase-activated receptor-2 (PAR-2) is present in vascular sm ooth muscle cells (SMC) and mediates mitogenesis. PAR-2 is activated by low concentrations of trypsin and the synthetic peptide SLIGRL. 2 Stimulation of bovine coronary artery SMC by trypsin (2 nM) caused a 3 fo ld increase in DNLA-synthesis. A similar effect was observed with 10 nM thr ombin. Trypsin-induced mitogenesis was inhibited by soybean trypsin inhibit or, indicating that the proteolytic activity of the enzyme was required for its mitogenic effect. 3 The specific PAR-2-activating peptide SLIGRL or the PAR1-activating pepti de SFFLRN did not elicit mitogenesis. 4 When the SMC were exposed to SLIGRL (40 nM), a homologous desensitization of cytosolic Ca2+ mobilization was found after subsequent stimulation with trypsin (40 nM) but not thrombin (15 nM). 5 Trypsin (2 nM) as well as SLIGRL (100 mu M) activated the nuclear factor kappa B (NF kappa B) with a maximum response 2 h after stimulation of the S MC. This suggests that both agonists acted via a common receptor, PAR-2. Ma ximum activation of NF kappa B by thrombin (10 nM) was detected after 4-5 h . 6 These data suggest that PAR-2 is present in coronary SMC and mediates a m itogenic response. Activation of NF kappa B via either PAR-1 or PAR-2 does not predict mitogenesis.