Magazine H I, Butt O, Yaghoutiel H R
Department of Biology, Queens College, Flushing, New York 11367, USA.
Am J Physiol. 1996 Jun;270(6 Pt 1):C1815-8. doi: 10.1152/ajpcell.1996.270.6.C1815.
The contribution of endothelin-1 (ET-1) and nitric oxide (NO) release to vascular contraction induced by synthetic peptide agonists of the alpha-thrombin receptor, TRAP-14 and TRAP-6, was evaluated with the use of rings of rat aorta. TRAP-6 induced fourfold greater contraction than that induced by addition of TRAP-14. TRAP-14, but not TRAP-6, stimulation of aortic rings resulted in a rapid (in seconds) and dose-dependent increase in ET-1 levels detected in the vessel perfusate. Release of ET-1 in vessels denuded of endothelium was indistinguishable from that of intact vessels, suggesting that endothelial cells are not required for the observed ET-1 release. The contractile potency of TRAP-14 was reduced in the presence of BQ-123, a specific antagonist of the endothelin A subtype of ET receptors, whereas TRAP-14 potency was increased significantly by pretreatment with the NO synthetase inhibitor NG-nitro-L-arginine (L-NNA). The contractile potency of TRAP-6 was not altered in the presence of BQ-123 or L-NNA, suggesting that TRAP-14 but not TRAP-6 potency is modulated by ET-1 and NO release. These data indicate that TRAP-6 has limited function relative to TRAP-14 and that thrombin receptor activation is not sufficient to induce ET-1 and NO release from rat aorta.
利用大鼠主动脉环，评估了内皮素-1（ET-1）和一氧化氮（NO）释放对凝血酶受体合成肽激动剂TRAP-14和TRAP-6诱导的血管收缩的作用。TRAP-6诱导的收缩比添加TRAP-14诱导的收缩大四倍。刺激主动脉环时，TRAP-14而非TRAP-6可导致在血管灌注液中检测到的ET-1水平迅速（数秒内）且呈剂量依赖性增加。在内皮剥脱的血管中ET-1的释放与完整血管中的释放无差异，这表明所观察到的ET-1释放不需要内皮细胞。在ET受体内皮素A亚型的特异性拮抗剂BQ-123存在的情况下，TRAP-14的收缩效力降低，而用NO合酶抑制剂NG-硝基-L-精氨酸（L-NNA）预处理可显著提高TRAP-14的效力。在BQ-123或L-NNA存在的情况下，TRAP-6的收缩效力未改变，这表明TRAP-14而非TRAP-6的效力受ET-1和NO释放的调节。这些数据表明，相对于TRAP-14，TRAP-6的功能有限，且凝血酶受体激活不足以诱导大鼠主动脉释放ET-1和NO。
