Nakahata N, Sato K, Abe M T, Nakanishi H
Department of Pharmacology, Fukushima Medical College, Japan.
Eur J Pharmacol. 1990 Aug 10;184(2-3):233-8. doi: 10.1016/0014-2999(90)90614-c.
Stimulation of thromboxane A2 (TXA2) receptors in human astrocytoma cells (1321N1) results in activation of phospholipase C via a pertussis toxin-insensitive G-protein. In the present study, the potency of a new TXA2 receptor antagonist, ONO NT-126, was examined with regard to receptor binding and phosphoinositide hydrolysis in human astrocytoma cells and was compared to that of the other known TXA2 antagonists. [3H]SQ29548 binding to membranes was inhibited by ONO NT-126 and the other TXA2 antagonists with Ki values (nM) of 0.09, 2.18, 8.35 and 25.9 for ONO NT-126, S-145, SQ29548 and ONO3708, respectively. STA2 and U46619, TXA2 receptor agonists, also inhibited [3H]SQ29548 binding with Ki (nM) of 25.1 and 233.5, respectively. STA2 and U46619 stimulated phosphoinositide hydrolysis in a concentration-dependent manner with EC50 values of 43.6 nM for STA2 and 1.2 microM for U46619, respectively. STA2 (1 microM)-induced phosphoinositide hydrolysis was also inhibited by TXA2 antagonists. The Ki values of TXA2 antagonists for the inhibition of phosphoinositide hydrolysis (nM) were 0.10 for ONO NT-126, 3.31 for S-145, 8.31 for SQ29548 and 19.49 for ONO3708 all of which were similar to those for receptor binding. The results indicate that ONO NT-126 is a potent and selective antagonist of TXA2 receptors in human astrocytoma cells.
刺激人星形细胞瘤细胞（1321N1）中的血栓素A2（TXA2）受体，会通过一种对百日咳毒素不敏感的G蛋白激活磷脂酶C。在本研究中，检测了新型TXA2受体拮抗剂ONO NT - 126在人星形细胞瘤细胞中的受体结合和磷酸肌醇水解方面的效力，并与其他已知的TXA2拮抗剂进行了比较。ONO NT - 126和其他TXA2拮抗剂均可抑制[3H]SQ29548与膜的结合，ONO NT - 126、S - 145、SQ29548和ONO3708的Ki值（nM）分别为0.09、2.18、8.35和25.9。TXA2受体激动剂STA2和U46619也可抑制[3H]SQ29548的结合，其Ki值（nM）分别为25.1和233.5。STA2和U46619以浓度依赖的方式刺激磷酸肌醇水解，STA2的EC50值为43.6 nM，U46619的EC50值为1.2 microM。STA2（1 microM）诱导的磷酸肌醇水解也受到TXA2拮抗剂的抑制。TXA2拮抗剂抑制磷酸肌醇水解的Ki值（nM），ONO NT - 126为0.10，S - 145为3.31，SQ29548为8.31，ONO3708为19.49，所有这些值与受体结合的值相似。结果表明，ONO NT - 126是一种强效且选择性的人星形细胞瘤细胞TXA2受体拮抗剂。
