二酰基甘油激酶抑制剂R59022可增强凝血酶刺激的人血小板的分泌及聚集。
A diacylglycerol kinase inhibitor, R59022, potentiates secretion by and aggregation of thrombin-stimulated human platelets.
作者信息
Nunn D L, Watson S P
机构信息
Department of Pharmacology, University of Oxford, U.K.
出版信息
Biochem J. 1987 May 1;243(3):809-13. doi: 10.1042/bj2430809.
Abstract
The diacylglycerol kinase inhibitor R59022 (10 microM) potentiates secretion and aggregation responses in human platelets challenged with sub-maximal concentrations of thrombin. Potentiation correlates closely with increased formation of diacylglycerol, increased phosphorylation of a 40 kDa protein, a known substrate for protein kinase C, and with decreased formation of phosphatidic acid, the product of diacylglycerol kinase. Phosphorylation of myosin light chains, formation of inositol phosphates and the mobilization of Ca2+ by thrombin are not affected by R59022 (10 microM). These data support a role for protein kinase C in platelet aggregation and secretion, and provide further evidence that endogenous diacylglycerols bring about the activation of this enzyme. These data also add further argument against a role for phosphatidic acid in platelet activation.
摘要
二酰基甘油激酶抑制剂R59022（10微摩尔）可增强在次最大浓度凝血酶刺激下的人血小板分泌和聚集反应。增强作用与二酰基甘油形成增加、一种40 kDa蛋白（蛋白激酶C的已知底物）的磷酸化增加以及二酰基甘油激酶产物磷脂酸的形成减少密切相关。肌球蛋白轻链的磷酸化、肌醇磷酸的形成以及凝血酶引起的Ca2+动员不受R59022（10微摩尔）影响。这些数据支持蛋白激酶C在血小板聚集和分泌中的作用，并进一步证明内源性二酰基甘油可导致该酶的激活。这些数据也进一步反驳了磷脂酸在血小板激活中的作用。
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