Smith J B, Dangelmaier C, Selak M A, Ashby B, Daniel J
Department of Pharmacology, Temple University Medical School, Philadelphia, PA 19140.
Biochem J. 1992 May 1;283 ( Pt 3)(Pt 3):889-92. doi: 10.1042/bj2830889.
The adhesion of platelets to collagen and their activation is the primary event in haemostasis. Following adhesion, platelet aggregation mediated by ADP, thromboxane A2 and thrombin leads to the formation of a platelet plug. It is known that platelet activation by each of these agonists involves an increase in the cytosolic free Ca2+ concentration, and this has been thought to be controlled by cyclic AMP. However, we report here that while signal transduction induced by ADP plus a thromboxane mimetic (U46619), or by thrombin, is inhibited by stimulators of adenylate cyclase such as a prostaglandin I2 (PGI2) analogue (Iloprost), PGD2 and forskolin, elevation of cyclic AMP does not inhibit either platelet adhesion to collagen or the associated Ca2+ mobilization, phosphatidic acid formation or 5-hydroxytryptamine secretion. Furthermore, collagen did not lower elevated levels of cyclic AMP in platelets measured in the presence of both a thromboxane antagonist and an ADP-removing system. The present results are discussed in the context of previous findings.
血小板与胶原蛋白的黏附及其激活是止血过程中的首要事件。黏附之后，由二磷酸腺苷（ADP）、血栓素A2和凝血酶介导的血小板聚集会导致血小板凝块的形成。已知这些激动剂中的每一种激活血小板都涉及胞质游离钙离子浓度的升高，并且这一直被认为是由环磷酸腺苷（cAMP）控制的。然而，我们在此报告，虽然由ADP加血栓素模拟物（U46619）或由凝血酶诱导的信号转导受到腺苷酸环化酶刺激剂如前列环素I2（PGI2）类似物（依洛前列素）、前列腺素D2和福斯高林的抑制，但cAMP升高既不抑制血小板与胶原蛋白的黏附，也不抑制相关的钙离子动员、磷脂酸形成或5-羟色胺分泌。此外，在存在血栓素拮抗剂和ADP去除系统的情况下测量，胶原蛋白并未降低血小板中升高的cAMP水平。本文结果结合先前的研究发现进行了讨论。
