Magazine H I, King J M, Srivastava K D
Department of Biology, Queens College, City University of New York, Flushing 11367, USA. HIM$
Int J Cardiol. 1996 Apr 26;53 Suppl:S75-80. doi: 10.1016/0167-5273(96)02569-7.
The effect of agonists of the known protease activated receptors (PAR), the thrombin and the PAR-2 receptors, on vasoactive mediator release and vascular tone were studied using rings of rat aorta. Stimulation of aortic rings with the thrombin receptor agonist, Trap-14, or the PAR-2 agonist, SLIGRL, resulted in a rapid release of nitric oxide. Trap-14 and SLIGRL-induced nitric oxide release was reduced by pre-treatment with BQ-788, an ETB endothelin receptor-specific antagonist. Consistent with a role for endothelin-1 receptor activation in Trap-14 and SLIGRL-induced nitric oxide release, endothelin-1 levels were increased significantly following 5 min treatment of aortic rings with Trap-14 or SLIGRL. Cumulative addition of Trap-14 to aortic rings denuded of endothelium resulted in dose-dependent contraction with an EC50 value of 23 +/- 5 microM, whereas SLIGRL addition failed to induce aortic contraction. These data suggest that the known protease activated receptors are functionally coupled to nitric oxide release. In addition, the thrombin receptor appears to modulate both vasodilator and contractile responses, whereas the PAR-2 receptor is linked only to vasodilation.
使用大鼠主动脉环研究了已知蛋白酶激活受体（PAR）的激动剂，即凝血酶和PAR-2受体，对血管活性介质释放和血管张力的影响。用凝血酶受体激动剂Trap-14或PAR-2激动剂SLIGRL刺激主动脉环，会导致一氧化氮迅速释放。用ETB内皮素受体特异性拮抗剂BQ-788预处理可减少Trap-14和SLIGRL诱导的一氧化氮释放。与内皮素-1受体激活在Trap-14和SLIGRL诱导的一氧化氮释放中所起的作用一致，用Trap-14或SLIGRL处理主动脉环5分钟后，内皮素-1水平显著升高。向去内皮的主动脉环中累积添加Trap-14会导致剂量依赖性收缩，EC50值为23±5微摩尔，而添加SLIGRL未能诱导主动脉收缩。这些数据表明，已知的蛋白酶激活受体在功能上与一氧化氮释放相关联。此外，凝血酶受体似乎既能调节血管舒张反应，又能调节收缩反应，而PAR-2受体仅与血管舒张有关。
