BQ-123 is a highly potent and selective endothelin A (ETA) receptor antagonist with an IC50 value of 7.3nM and a Ki value of 25nM[1]. BQ-123 is a cyclic pentapeptide first isolated from the fermentation broth of Streptomyces misakiensis in 1991[2]. BQ123 can effectively reverse ischemic acute renal failure and increase the reabsorption of sodium ions by proximal tubular cells[3].
In vitro, BQ-123 (12mM) treatment of rat brain primary cultures for 48h increased the number of β-III tubulin-positive neurons under normoxic conditions and reduced neuronal loss under hypoxic conditions[4].
In vivo, BQ-123 (3mg/kg) was intravenously injected into rats with pentylenetetrazol (PTZ)-induced tonic-clonic epilepsy, significantly delayed the onset of epilepsy in rats, significantly reversed the oxidative effects of PTZ on brain tissue, and increased neuronal chromatin in the dentate gyrus of the hippocampus[5]. BQ-123 (0.16-164nM/kg/min) was treated with continuous intravenous infusion for 6h in spontaneously hypertensive rats (SHR) and reduced mean arterial pressure in a dose-dependent manner[6].
References:
[1] Ihara M, Ishikawa K, Fukuroda T, et al. In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor[J]. Journal of cardiovascular pharmacology, 1992, 20: S11-S14.
[2] Peishoff C E, Janes R W, Wallace B A. Comparison of the structures of the endothelin A receptor antagonists BQ123 and N-methyl leucine BQ123 with the crystal structure of the C-terminal tail of endothelin-1[J]. FEBS letters, 1995, 374(3): 379-383.
[3] Sheridan A M, Bonventre J V. Pathophysiology of ischemic acute renal failure[J]. Blood Purification in Intensive Care, 2001, 132: 7-21.
[4] Danielyan L, Mueller L, Proksch B, et al. Similar protective effects of BQ-123 and erythropoietin on survival of neural cells and generation of neurons upon hypoxic injury[J]. European journal of cell biology, 2005, 84(11): 907-913.
[5] Erdogan H, Ekici F, Katar M, et al. The protective effects of endothelin-A receptor antagonist BQ-123 in pentylenetetrazole-induced seizure in rats[J]. Human & experimental toxicology, 2014, 33(10): 1008-1016.
[6] Douglas S A, 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]. Journal of hypertension, 1994, 12(5): 561-568.
BQ-123是一种高效、选择性内皮素A（ETA）受体拮抗剂，IC50 值为7.3nM，Ki值为25nM[1]。BQ-123是1991年首次从Misakiensis链霉菌的发酵液中分离的环状五肽[2]。BQ123可有效逆转缺血性急性肾衰竭，能增加近端小管细胞对钠离子的重吸收[3]。
在体外，BQ-123（12mM）处理大鼠脑原代培养物48h，在常氧条件下增加了β-III微管蛋白阳性神经元的数量，在缺氧条件下减少了神经元损失[4]。
在体内，BQ-123（3mg/kg）通过静脉注射治疗戊四唑（PTZ）诱导的强直-阵挛性癫痫大鼠，显著延迟了大鼠癫痫发作时间，显著逆转了PTZ对脑组织的氧化作用，增加了海马齿状回区的神经元染色质[5]。BQ-123（0.16-164nM/kg/min）通过静脉注射持续输注6h治疗自发性高血压大鼠（SHR），剂量依赖性地降低了平均动脉压[6]。