血小板激活因子受体拮抗剂WEB 2086在体外对牛体内PAF诱导的血小板聚集的抑制作用。

Inhibition of PAF-induced platelet aggregation by WEB 2086 'in-vitro', an antagonist to the receptor for platelet-activating factor, in bovine.

作者信息

da Silva M B, Herion F, Raskinet R, David J L, Gustin P, Dessy C, Lekeux P

机构信息

Laboratory for Functional Investigation, Faculty of Veterinary Medicine, University of Liège, Belgium.

出版信息

Zentralbl Veterinarmed A. 1996 Sep;43(7):399-413. doi: 10.1111/j.1439-0442.1996.tb00468.x.

DOI:10.1111/j.1439-0442.1996.tb00468.x

PMID:8921726

Abstract

The sensitivity of bovine platelet aggregation in response to PAF stimulation and the ability of WEB 2086 (a thieno-triazolodiazepine) to inhibit response to PAF-induced platelet aggregation were investigated in the blood from five healthy male Belgian Blue calves. The recorded response to PAF showed a plateau which was dependent on the PAF concentration. Platelet aggregation induced by PAF consists of two mechanisms: reversible and irreversible aggregations which are accompanied by the release of platelet granule contents. Reversible aggregation occurred above (2 . 10(-9) mol/l) PAF, and irreversible aggregation occurred above (2 . 10(-7) mol/l) PAF. Addition of WEB 2086 to bovine platelets in vitro induced a rightward shift in the dose-response curve to PAF. WEB 2086 inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.61). The results of our study show that PAF induces platelet aggregation in platelet-rich plasma (PRP) and that addition of WEB 2086 to bovine platelets in vitro inhibits PAF-induced Platelet Aggregation.

摘要

研究了5头健康雄性比利时蓝牛犊血液中牛血小板对血小板活化因子（PAF）刺激的聚集敏感性以及WEB 2086（一种噻吩并三唑二氮杂卓）抑制PAF诱导的血小板聚集反应的能力。记录到的对PAF的反应呈现出一个依赖于PAF浓度的平台期。PAF诱导的血小板聚集由两种机制组成：可逆性聚集和不可逆性聚集，且伴有血小板颗粒内容物的释放。可逆性聚集在PAF浓度高于（2×10⁻⁹摩尔/升）时发生，不可逆性聚集在PAF浓度高于（2×10⁻⁷摩尔/升）时发生。在体外将WEB 2086添加到牛血小板中会导致对PAF的剂量反应曲线向右移动。WEB 2086以竞争性可逆方式抑制PAF诱导的聚集（pA2 = 7.61）。我们的研究结果表明，PAF在富含血小板血浆（PRP）中诱导血小板聚集，并且在体外将WEB 2086添加到牛血小板中可抑制PAF诱导的血小板聚集。