Evidence for proteinase-activated receptor-2 (PAR-2)-mediated mitogenesis in coronary artery smooth muscle cells
Evidence for proteinase-activated receptor-2 (PAR-2)-mediated mitogenesis in coronary artery smooth muscle cells
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DOI：
10.1038/sj.bjp.0702509
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发表时间：
1999-04-01
影响因子：
7.3
通讯作者：
Schrör, K
中科院分区：
文献类型：
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作者：
Bretschneider, E;Kaufmann, R;Schrör, K
1本研究探讨了在血管平滑肌细胞（SMC）中是否存在凝血酶受体（PAR-1）和蛋白酶激活受体2（PAR-2），并介导有丝分裂。PAR-2被低浓度的胰蛋白酶和合成肽SLIGRL激活。2胰蛋白酶（2 nM）刺激牛冠状动脉SMC导致DNLA合成增加3倍。用10 nM凝血酶观察到类似的效果。胰蛋白酶诱导的有丝分裂被大豆胰蛋白酶抑制剂抑制，表明酶的蛋白水解活性是其促有丝分裂作用所必需的。3特异性PAR-2激活肽SLIGRL或PAR 1激活肽SFFLRN不诱导有丝分裂。4当SMC暴露于SLIGRL（40 nM）时，在随后用胰蛋白酶（40 nM）刺激后发现胞质Ca 2+动员的同源脱敏，但凝血酶（15 nM）没有。5胰蛋白酶（2 nM）以及SLIGRL（100 μ M）激活核因子κ B（NF κ B B）的最大反应后2小时刺激SMC。这表明两种激动剂通过共同的受体PAR-2起作用。4-5 h后检测到凝血酶（10 nM）对NF κ B的最大激活。6这些数据表明，PAR-2存在于冠状动脉SMC中，并介导促有丝分裂反应。通过PAR-1或PAR-2激活NF κ B不能预测有丝分裂。
1 This study investigates, whether in addition to the thrombin receptor (PAR-1), the proteinase-activated receptor-2 (PAR-2) is present in vascular smooth 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 fold increase in DNLA-synthesis. A similar effect was observed with 10 nM thrombin. Trypsin-induced mitogenesis was inhibited by soybean trypsin inhibitor, 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 peptide 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 SMC. This suggests that both agonists acted via a common receptor, PAR-2. Maximum 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 mitogenic response. Activation of NF kappa B via either PAR-1 or PAR-2 does not predict mitogenesis.