苯二氮䓬受体配体RO 5-4864和RO 15-1788不会阻断用海曲替林WEB2086观察到的对PAF诱导的血小板聚集的抑制作用。

The benzodiazepine receptor ligands RO 5-4864 and RO 15-1788 do not block the inhibition of PAF-induced platelet aggregation seen with the hetrazepine WEB2086.

作者信息

Griffin K, Hong T, Levy J V

机构信息

Laboratory of Pharmacology and Experimental Therapeutics, Pacific Presbyterian Medical Center/MRI, San Francisco, CA 94115.

出版信息

Biochem Biophys Res Commun. 1989 Apr 14;160(1):263-7. doi: 10.1016/0006-291x(89)91650-1.

DOI:10.1016/0006-291x(89)91650-1

PMID:2540748

Abstract

The hypothesis was tested that the hetrazepine WEB 2086 acts as an inhibitor of PAF-induced platelet aggregation via interaction with the platelet benzodiazepine receptor(BDZR). WEB 2086 is a potent inhibitor of rabbit platelet aggregation and ATP secretion induced by 370 nM PAF. The two BDZR ligands RO 5-4864 and RO 15-1788 (7-96 microM) are inactive as PAF antagonists. When platelets were pretreated with either BDZR ligand, and then exposed to various concentrations of WEB 2086, there was no alteration of the dose-response relationship of the hetrazepine on PAF-induced aggregation, as reflected by threshold concentration, ED50, or maximum inhibition seen with WEB 2086. Pretreatment of platelets with the BDZR ligands also failed to block the inhibitory action of WEB 2086 on PAF-induced ATP release. The data are consistent with the notion that WEB 2086 acts as a PAF antagonist through its action at a specific PAF receptor, and is dissociated from, and independent of, interaction with the benzodiazepine receptor.

摘要

有这样一个假设需要验证

海曲替平WEB 2086通过与血小板苯二氮䓬受体（BDZR）相互作用，作为血小板活化因子（PAF）诱导的血小板聚集的抑制剂。WEB 2086是370 nM PAF诱导的兔血小板聚集和ATP分泌的有效抑制剂。两种BDZR配体RO 5-4864和RO 15-1788（7-96 microM）作为PAF拮抗剂无活性。当血小板先用任何一种BDZR配体预处理，然后再暴露于不同浓度的WEB 2086时，海曲替平对PAF诱导的聚集的剂量反应关系没有改变，这可通过阈值浓度、半数有效量（ED50）或WEB 2086所见的最大抑制来反映。用BDZR配体对血小板进行预处理也未能阻断WEB 2086对PAF诱导的ATP释放的抑制作用。这些数据与以下观点一致：WEB 2086通过作用于特定的PAF受体而作为PAF拮抗剂起作用，并且与苯二氮䓬受体的相互作用无关且独立。