Tranquille N, Emeis J J
Gaubius Laboratory IVVO-TNO, Leiden, Netherlands.
Eur J Pharmacol. 1992 Mar 24;213(2):285-92. doi: 10.1016/0014-2999(92)90693-x.
Using a perfused rat hindleg system, release of tissue-type plasminogen activator (t-PA) from endothelial cells could be induced by platelet-activating factor (PAF), bradykinin, substance P, thrombin, carbachol and A23187, while this release was inhibited by mepacrine and by nor-dihydroguaiaretic acid. The PAF-induced release of t-PA was inhibited by the cytochrome P-450 mono-oxygenase inhibitors, metyrapone, ketoconazole and SKF 525A and by eicosatetraynoic acid but not by indomethacin or BW 755C, suggesting the involvement of epoxygenase products. The PAF-induced release of von Willebrand factor (vWF) was also similarly inhibited by the cytochrome P-450 monooxygenase inhibitor, ketoconazole. Phorbol ester and phospholipase C induced the release of both t-PA and vWF, while phospholipase A2 did not. The release induced by PAF and bradykinin was not influenced by pretreatment with pertussis toxin.
利用灌注大鼠后肢系统，血小板激活因子（PAF）、缓激肽、P物质、凝血酶、卡巴胆碱和A23187可诱导内皮细胞释放组织型纤溶酶原激活物（t-PA），而米帕林和去甲二氢愈创木酸可抑制这种释放。细胞色素P-450单加氧酶抑制剂美替拉酮、酮康唑和SKF 525A以及二十碳四炔酸可抑制PAF诱导的t-PA释放，但吲哚美辛或BW 755C无此作用，提示环氧合酶产物参与其中。细胞色素P-450单加氧酶抑制剂酮康唑也同样抑制PAF诱导的血管性血友病因子（vWF）释放。佛波酯和磷脂酶C可诱导t-PA和vWF释放，而磷脂酶A2则不能。百日咳毒素预处理不影响PAF和缓激肽诱导的释放。
