Protein Kinase C Activators and Contractile Responses to Lead in Rabbit Arteries

研究铅及蛋白激酶C的激活剂在收缩过程中对钙信号系统的影响。制各家兔肠系膜动脉血管条，悬吊于浴槽中．其张力变化经换能并放大后描记于记录仪上。实验中观察到leadacetate（10-10～10-3mol／L）能使之产生收缩（ED50为10－5mol／L）。这种收缩可被蛋白激酶C激动剂TPA及Mezarin加强而导致剂量反应曲线的左移。无活性的TPA缺乏此种作用。而蛋白激酶C的选择性抑制剂H7则可阻抑这种收缩。在无钙溶液中leadacetate不再引起动脉条的收缩。verapamil则可减低铅引起的收缩。去除血管内皮对铅收缩并无影响、本文表明铅引起的收缩与钙信号系统中蛋白激酶C这一环节有密切关系。

Protein Kinase C Activators and Contractile Responses to Lead in Rabbit Arteries

We studied the actions of lead and enzyme activators on this branch of the calcium messenger system. Helically-cut strips of rabbit mesenteric artery were mounted in muscle baths for measurement of isometric force development.Cumulative addition of lead acetate (10-10 to 10-3 mol/L ) to the muscle bath induced contractions (ED50 value = 10 -5 mol/ L). These contractile responses to lead acetate were potentinted by protein kinase C activators, phorbol 12-myristate 13-acetate (TPA ) and mezerein as indicated by leftward shifts in the dose-response curve. H-7, a selective blocker of protcin kinase C, inhibited contractions to lead acetate. The inactive phorbol ester, phorbol 12-myristate 13-acetate 4-0-mcthyl ether, did not alter contractile responses to the metal. Arteries incubated in calcium-free solution did not contract by lead acetate and verapamil decreased lead-induced contractions. Contractile responses to lead acetate in arteries denuded of endothelium did not differ from those in intact vessels. These data indicate that lead interacts with the protein kinase C pathway of the calcium messenger system in vascular smooth muscle cells to induce contraction.