BQ-123

BQ-123是一种强效的和选择性的ETA内皮素受体拮抗剂,作用于ETA和ETB受体的Ki值分别为1.4和1500 nM.

内皮素受体是一种G蛋白偶联受体.ETA受体增加细胞内游离Ca2+.另外,ETA受体的激活增加血管收缩和血压.

BQ-123是一种选择性的ETA受体拮抗剂.在表达ETA的细胞中,BQ 123(10-6 M)抑制内皮素-1(ET-1)(10-6 M)诱导的[Ca2 +] i增加达95%[1].在大鼠血管平滑肌细胞(VSMC)中,BQ-123抑制ET-1诱导的ET-1受体结合\细胞收缩\[Ca2 +]i动员\[3H]胸苷掺入\MAP激酶激活和MTT还原.然而,BQ-123不抑制血管紧张素II(ANG II)和精氨酸加压素(AVP)诱导的MAP激酶活性及[Ca2 +]i动员的增加[2].

在自发性高血压大鼠(SHR)\肾素高血压大鼠和正常血压大鼠中,BQ-123(16 nM/kg/min)剂量依赖性地降低SHR中的平均动脉压.此外,BQ-123降低肾素高血压大鼠和正常血压大鼠血压[3].在再灌注损伤肾脏移植大鼠模型中,BQ-123防止再灌注损伤并抑制ET-1,2的合成和释放[4].

参考文献：
[1].  Sakamoto A, Yanagisawa M, Sawamura T, et al. Distinct subdomains of human endothelin receptors determine their selectivity to endothelinA-selective antagonist and endothelinB-selective agonists. J Biol Chem, 1993, 268(12): 8547-8553.
[2].  Guo X, Okada K, Fujita N, et al. Inhibitory effect of BQ-123 on endothelin-1-stimulated mitogen-activated protein kinase and cell growth of rat vascular smooth muscle cells. Hypertens Res, 1996, 19(1): 23-30.
[3].  Douglas SA, Gellai M, Ezekiel M, et al. BQ-123, a selective endothelin subtype A-receptor antagonist, lowers blood pressure in different rat models of hypertension. J Hypertens, 1994, 12(5): 561-567.
[4].  Büyükgebiz O, Aktan AO, Haklar G, et al. BQ-123, a specific endothelin (ETA) receptor antagonist, prevents ischemia-reperfusion injury in kidney transplantation. Transpl Int, 1996, 9(3): 201-207.