BQ-123

BQ-123 is a potent and selective antagonist of ETA endothelin receptor with Ki values of 1.4 and 1500 nM for ETA and ETB receptors, respectively.

Endothelin receptor is a G protein-coupled receptor. ETA receptor increases intracellular-free Ca2+. Also, Activation of ETA receptor increases vasoconstriction and blood pressure.

BQ-123 is a selective ETA receptor antagonist. In the ETA-expressing cells, BQ123 (10-6 M) inhibited endothelin-1 (ET-1) (10-6 M)-induced [Ca2+]i increase by 95% [1]. In rat vascular smooth muscle cells (VSMC), BQ-123 inhibited ET-1 receptor binding, cellular contraction, [Ca2+ ]i mobilization, [3H]thymidine incorporation, MAP kinase activation and MTT reduction induced by ET-1. However, BQ-123 didn’t inhibit angiotensin II (Ang II)- and arginine vasopressin (AVP)-induced increases in MAP kinase activity and [Ca2+]i mobilization [2].

In spontaneously hypertensive rats (SHR), renin hypertensive rats and normotensive rats, BQ-123 (16 nM/kg/min) reduced mean arterial pressure in a dose-dependent way in SHR. Also, BQ-123 lowered blood pressure in both renin hypertensive rats and normotensive rats [3]. In a kidney transplantation rat model with reperfusion injury, BQ-123 prevented reperfusion injury and inhibited the synthesis and release of ET-1,2 [4].

References:
[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.