Kuo B S, Dryjski M, Bjornsson T D
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Thromb Haemost. 1989 Feb 28;61(1):70-6.
The effects of nicotine and its major metabolite, cotinine, were evaluated on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in cultured bovine aortic endothelial cells. Both compounds increased PA secretion, determined by 125I fibrin plate assay, in a time- and dose-dependent manner. Maximum effects after 24 hr incubation were observed for nicotine at 10(-8) M and for cotinine at 10(-7) M, which corresponded to about 2.6-fold increases over control for both compounds. The pharmacological PA stimulation required both RNA and protein syntheses, as evidenced by inhibition by actinomycin D and cycloheximide. Both control and treated cells produced multiple forms of PA, as evaluated by SDS-PAGE zymography, and a single form of PAI, as evidenced by reverse fibrin autography. Although activities of all species of PA were enhanced by nicotine and cotinine, these compounds had no significant effects on the release of PAI. These results thus suggest that nicotine and cotinine may have fibrinolytic activity in vivo.
研究了尼古丁及其主要代谢产物可替宁对培养的牛主动脉内皮细胞中纤溶酶原激活物（PA）和纤溶酶原激活物抑制剂（PAI）分泌的影响。通过125I纤维蛋白平板试验测定，这两种化合物均以时间和剂量依赖性方式增加PA分泌。孵育24小时后，观察到尼古丁在10^(-8) M时和可替宁在10^(-7) M时产生最大效应，两种化合物相对于对照均增加了约2.6倍。放线菌素D和环己酰亚胺的抑制作用证明，药理学上PA的刺激需要RNA和蛋白质合成。通过SDS-PAGE酶谱分析评估，对照细胞和处理细胞均产生多种形式的PA，通过反向纤维蛋白自显影证明产生单一形式的PAI。尽管尼古丁和可替宁增强了所有PA种类的活性，但这些化合物对PAI的释放没有显著影响。因此，这些结果表明尼古丁和可替宁在体内可能具有纤溶活性。
