Inhibition of binding of the platelet-activating factor AGEPC to platelets by the AGEPC analog rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate (CV-3988).
Inhibition of binding of the platelet-activating factor AGEPC to platelets by the AGEPC analog rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate (CV-3988).
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AGEPC 类似物 rac-3-(N-n-十八烷基氨基甲酰氧基)-2-甲氧基丙基 2-噻唑基乙基磷酸酯 (CV-3988) 可抑制血小板激活因子 AGEPC 与血小板的结合。
DOI：
10.1016/0006-291x(85)90634-5
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发表时间：
1985
影响因子：
3.1
通讯作者：
Valone,FH
中科院分区：
文献类型：
--
作者：
Valone,FH
摘要 CV-3988，rac-3-(Nn-十八烷基氨基甲酰氧基)-2-甲氧基丙基 2-噻唑基乙基磷酸酯，是 1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱（AGEPC 或 PAF 乙醚）血小板激活活性的特异性抑制剂。 CV-3988 浓度在 10− 8 和 10− 7 M 之间，以剂量相关的方式抑制 AGEPC 诱导的洗涤人血小板聚集（IC 50= 2.9±1.1× 10− 8 M CV-3988），而 CV-3988 浓度高达 4× 10− 6 M 并不会减少凝血酶或二磷酸腺苷引起的血小板聚集。 CV-3988 以浓度依赖性方式抑制 [3 H] AGEPC 与血小板的结合 (IC 50= 6.7±1.8× 10− 8 M)。与 AGEPC 相比，CV-3988 对 AGEPC 受体的亲和力低 1000 倍。通过对孵育四小时后从血小板悬浮液中提取的[3H]AGEPC进行薄层色谱分析评估，CV-3988不会刺激AGEPC的血小板代谢。因此，这些研究表明，CV-3988 通过抑制 AGEPC 与其特定血小板受体的结合来抑制 AGEPC 激活血小板。
Abstract CV-3988, rac-3-(Nn-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate, is a specific inhibitor of the platelet-activating activity of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine (AGEPC or PAF acether). Concentrations of CV-3988 between 10− 8 and 10− 7 M inhibited AGEPC-induced aggregation of washed human platelets in a dose-related manner (IC 50= 2.9±1.1× 10− 8 M CV-3988) whereas concentrations of CV-3988 as high as 4× 10− 6 M did not diminish platelet aggregation by thrombin or adenosine diphosphate. The binding of [3 H] AGEPC to platelets was inhibited by CV-3988 in a concentration-dependent manner (IC 50= 6.7±1.8× 10− 8 M). Compared to AGEPC, CV-3988 has a 1000-fold lower affinity for the AGEPC receptor. CV-3988 did not stimulate platelet metabolism of AGEPC as assessed by thin-layer chromatographic analysis of [3 H] AGEPC extracted from platelet suspensions after four hours of incubation. Thus these studies indicate that CV-3988 inhibits platelet activation by AGEPC by inhibiting binding of AGEPC to its specific platelet receptor.