血小板激活因子拮抗剂WEB 2086对豚鼠气道微血管渗漏及人血小板聚集的影响。
Effect of a Paf antagonist, WEB 2086, on airway microvascular leakage in the guinea-pig and platelet aggregation in man.
作者信息
Evans T W, Dent G, Rogers D F, Aursudkij B, Chung K F, Barnes P J
机构信息
Department of Clinical Pharmacology, Brompton Hospital, London.
出版信息
Br J Pharmacol. 1988 May;94(1):164-8. doi: 10.1111/j.1476-5381.1988.tb11511.x.
Abstract
- The triazolodiazepine WEB 2086 has been evaluated as an antagonist of platelet-activating factor (Paf) by studying its effects on Paf-induced human platelet aggregation and microvascular leakage in guinea-pigs. 2. WEB 2086 inhibited Paf-induced platelet aggregation in platelet-rich plasma in vitro (IC50 = 117 +/- 35 nM, mean +/- s.d.) but had no effect on adenosine 3',5'-diphosphate-induced aggregation. 3. Paf-induced microvascular leakage, measured by the extravasation of intravenously-injected Evans blue dye, was inhibited in a dose-related fashion in the airways and other tissues by WEB 2086, achieving a maximal inhibitory effect at 10 micrograms kg-1, i.v. 4. However, WEB 2086 (10 micrograms kg-1, i.v.) did not inhibit a comparable increase in vascular permeability induced by ovalbumin in sensitized guinea-pigs. 5. We conclude that WEB 2086 is a potent antagonist of Paf and that Paf does not appear to be responsible for antigen-induced microvascular leakage.
摘要
- 通过研究三唑并二氮杂卓类药物WEB 2086对血小板活化因子（Paf）诱导的人血小板聚集及豚鼠微血管渗漏的影响，对其作为Paf拮抗剂进行了评估。2. WEB 2086在体外可抑制富含血小板血浆中Paf诱导的血小板聚集（IC50 = 117 +/- 35 nM，平均值 +/- 标准差），但对腺苷3',5'-二磷酸诱导的聚集无影响。3. 通过静脉注射伊文思蓝染料外渗来测量，Paf诱导的微血管渗漏在气道和其他组织中被WEB 2086以剂量相关方式抑制，静脉注射10微克/千克时达到最大抑制效果。4. 然而，静脉注射10微克/千克的WEB 2086并未抑制致敏豚鼠中由卵清蛋白诱导的类似血管通透性增加。5. 我们得出结论，WEB 2086是一种有效的Paf拮抗剂，且Paf似乎并非抗原诱导的微血管渗漏的原因。
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