Sannomiya Y, Tatsumi N, Okuda K
Department of Laboratory Medicine, Osaka City University Medical School, Japan.
Biochem Int. 1988 Dec;17(6):1059-70.
We examined the effects of two inhibitors of aggregation of human platelets the, Forskolin and Cilostazol on clot retraction. Both substances suppressed clot retraction in a dose-dependent way. Both suppress platelet aggregation because of an increase in intercellular cyclic AMP, but there was no close correlations were shown between suppression rate for clot retraction and cyclic-AMP content in platelets in the clot in each substance. Furthermore, although it has been considered that actomyosin in platelets is a major contractile source for clot retraction and that failure of actin polymerization results suppression of clot retraction. As it was difficult to obtain active actin from platelets of the reagents on the polymerization. Cilostazol accelerated actin polymerization, whereas Forskolin did not. From these findings, it was considered that the effects of both substances on clot retraction could not be interpreted directly just by the increasing effect for intracellular cyclic-AMP. Clot retraction is consider to be a in vitro model of hemostasis and its contractile force is supplied from platelets (1,2,3). Experiments used prostaglandin E-1 revealed that elevation of cyclic-AMP (c-AMP) would regulate the clot retraction, and experiments used cytochalasin B demonstrated that actomyosin is responsible to the retraction (4,5). Many date demonstrate that elevation of c-AMP level suppresses platelet aggregation (6,7). c-AMP, therefore, should play a key role on platelet activation. Forskolin and Cilostazol are newly-developed reagents as a suppress for platelet functions. Pharmacological action of these substances have been interpreted to process increase effect for intracellular c-AMP of platelets(8,9). If so, both substances should show some effect on clot retraction. Under this assumption, we examined the effects.
我们研究了两种人血小板聚集抑制剂——福斯高林和西洛他唑对血凝块回缩的影响。两种物质均以剂量依赖的方式抑制血凝块回缩。二者均因细胞间环磷酸腺苷（cAMP）增加而抑制血小板聚集，但每种物质中血凝块回缩的抑制率与血凝块中血小板的环磷酸腺苷含量之间未显示出密切相关性。此外，尽管人们认为血小板中的肌动球蛋白是血凝块回缩的主要收缩来源，且肌动蛋白聚合失败会导致血凝块回缩受到抑制。但由于难以从试剂处理的血小板中获得活性肌动蛋白用于聚合反应。西洛他唑可加速肌动蛋白聚合，而福斯高林则不能。基于这些发现，认为这两种物质对血凝块回缩的影响不能仅仅通过细胞内环磷酸腺苷的增加效应来直接解释。血凝块回缩被认为是止血的体外模型，其收缩力由血小板提供（1,2,3）。使用前列腺素E-1的实验表明，环磷酸腺苷（c-AMP）升高会调节血凝块回缩，使用细胞松弛素B的实验表明，肌动球蛋白负责回缩（4,5）。许多数据表明，c-AMP水平升高会抑制血小板聚集（6,7）。因此，c-AMP在血小板激活中应起关键作用。福斯高林和西洛他唑是新开发的作为血小板功能抑制剂的试剂。这些物质的药理作用被解释为对血小板细胞内c-AMP有增加作用（8,9）。如果是这样，这两种物质应该对血凝块回缩有一定作用。在这一假设下，我们研究了它们的影响。
