Wilde J I, Retzer M, Siess W, Watson S P
Department of Pharmacology, University of Oxford, UK.
Platelets. 2000 Aug;11(5):286-95. doi: 10.1080/09537100050129305.
Shape change is an important early event in platelet activation. In this study we show that the Ca2+ chelator BAPTA and the Rho-kinase inhibitor Y-27632 inhibit ADP-induced myosin light chain (MLC) phosphorylation and platelet shape change through distinct pathways and with distinct kinetics. Ca2+ is largely responsible for the initial onset of shape change, whilst Rho-kinase plays a major role in the maintenance of the response. The relative contribution of these two pathways to each stage of the response was dependent on the method of platelet preparation, but in all cases shape change was shown to be downstream of the P2Y1 receptor. Similar observations were made in murine platelets. The shape change response was modulated via changes in cAMP levels, possibly via the P2TAC receptor, but not by tyrosine phosphorylation. We conclude that ADP-induced shape change occurs via the P2Y1 receptor, which can be differentially coupled to Rho-kinase and Ca2+-linked pathways dependent on the method of platelet preparation.
形态变化是血小板激活过程中的一个重要早期事件。在本研究中，我们表明Ca2+螯合剂BAPTA和Rho激酶抑制剂Y-27632通过不同途径和不同动力学抑制ADP诱导的肌球蛋白轻链（MLC）磷酸化和血小板形态变化。Ca2+在很大程度上负责形态变化的初始发生，而Rho激酶在维持反应中起主要作用。这两条途径对反应各阶段的相对贡献取决于血小板制备方法，但在所有情况下，形态变化都显示在P2Y1受体的下游。在小鼠血小板中也有类似的观察结果。形态变化反应通过cAMP水平的变化进行调节，可能是通过P2TAC受体，但不是通过酪氨酸磷酸化。我们得出结论，ADP诱导的形态变化通过P2Y1受体发生，根据血小板制备方法的不同，该受体可与Rho激酶和Ca2+相关途径发生不同的偶联。
