BQ-788 is a selective nonpeptide endothelin type B (ETB) receptor antagonist with an IC50 of 1.2nM[1]. BQ-788 can specifically bind to ETB receptors, blocking the interaction between endothelin and its receptors, thereby inhibiting endothelin-mediated effects such as vasoconstriction and cell proliferation[2]. BQ-788 is used to investigate the mechanisms of ETB in the cardiovascular system, including diseases like hypertension and heart failure[3]. BQ-788 can also be used to study the role of ETB in the nervous system, such as neuroprotection and neuroinflammation[4].
In vitro, BQ-788 (1μM) co-treated with fibrinogen (Fg; 4mg/mL) in rat heart microvascular endothelial cells (RHMECs) for 45 minutes significantly attenuated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK-1/2) induced by Fg[5]. BQ-788 (10μM) pre-treated rat olfactory mucosa cells for 1 week had no significant effect on cell proliferation but significantly increased the expression level of endogenous endothelin-1 (ET-1)[6].
In vivo, BQ-788 (0.2, 1, and 5mg/kg) was intravenously injected into ICR mice, followed by stimulation with ET-1 (0.1μmol/kg), and BQ-788 significantly inhibited ET-1-induced bronchoconstriction in mice[7]. BQ-788 (30nmol) co-injected subcutaneously with ET-1 (100pmol) into C57BL/6J mice significantly enhanced ET-1-induced scratching behavior[8].
References:
[1] Okada M, Nishikibe M. BQ-788, a selective endothelin ET(B) receptor antagonist. Cardiovasc Drug Rev. 2002 Winter;20(1):53-66.
[2] O'Donnell SR, Kay CS. Effects of endothelin receptor selective antagonists, BQ-123 and BQ-788, on IRL 1620 and endothelin-1 responses of airway and vascular preparations from rats. Pulm Pharmacol. 1995 Feb;8(1):11-9.
[3] Schroeder RL, Keiser JA, Cheng XM, et al. PD 142893, SB 209670, and BQ 788 selectively antagonize vascular endothelial versus vascular smooth muscle ET(B)-receptor activity in the rat. J Cardiovasc Pharmacol. 1998 Dec;32(6):935-43.
[4] Costa RA, Amatnecks JA, de Oliveira Guaita G, et al. Sexual dimorphism of hypothalamic serotonin release during systemic inflammation: Role of endothelin-1. J Neuroimmunol. 2024 Sep 15;394:578427.
[5] Sen U, Tyagi N, Patibandla PK, et al. Fibrinogen-induced endothelin-1 production from endothelial cells. Am J Physiol Cell Physiol. 2009 Apr;296(4):C840-7.
[6] Bryche B, Saint-Albin A, Le Poupon Schlegel C, et al. Endothelin increases the proliferation of rat olfactory mucosa cells. Neural Regen Res. 2020 Feb;15(2):352-360.
[7] Nagase T, Aoki T, Oka T, et al. ET-1-induced bronchoconstriction is mediated via ETB receptor in mice. J Appl Physiol (1985). 1997 Jul;83(1):46-51.
[8] Liang J, Kawamata T, Ji W. Molecular signaling of pruritus induced by endothelin-1 in mice. Exp Biol Med (Maywood). 2010 Nov;235(11):1300-5.
BQ-788是一种选择性非肽类内皮素B型（ETB）受体拮抗剂，IC50为1.2nM[1]。BQ-788可以特异性地与ETB受体结合，阻断内皮素与其受体的相互作用，从而抑制内皮素介导的血管收缩、细胞增殖等效应[2]。BQ-788被用于研究ETB在心血管系统中的作用机制，包括高血压、心力衰竭等疾病[3]。BQ-788还可用于研究ETB在神经系统中的作用，如神经保护、神经炎症等方面[4]。
在体外，BQ-788（1μM）与纤维蛋白原（Fg；4mg/mL）共同处理大鼠心肌微血管内皮细胞（RHMECs）45min，BQ-788显著减弱Fg诱导的细胞外信号调节激酶1/2（ERK-1/2）的磷酸化水平[5]。BQ-788（10μM）预处理大鼠嗅黏膜细胞1周，对细胞增殖无显著影响，可显著增加细胞内源性内皮素-1（ET-1）的表达水平 [6]。
在体内，BQ-788（0.2、1、5mg/kg）静脉注射ICR小鼠，随后以ET-1（0.1μmol/kg）刺激小鼠，BQ-788显著抑制ET-1诱导的小鼠气道收缩[7]。BQ-788（30nmol）与ET-1（100pmol）共同皮下注射至C57BL/6J小鼠，BQ-788显著增强ET-1诱导的抓挠行为[8]。