Vial Catherine, Pitt Samantha J, Roberts Jon, Rolf Michael G, Mahaut-Smith Martyn P, Evans Richard J
Department of Cell Physiology and Pharmacology, University of Leicester, University Rd, Leicester LE1 9HN, United Kingdom.
Blood. 2003 Nov 15;102(10):3646-51. doi: 10.1182/blood-2003-06-1963. Epub 2003 Aug 7.
Purine nucleotides acting through P2 receptors play key roles in platelet signaling. The P2X1 receptor is an adenosine triphosphate (ATP)-gated ion channel that mediates a rapid calcium influx signal, but can also synergize with subsequent adenosine diphosphate (ADP)-evoked P2Y1 receptor-mediated responses and thus may contribute to platelet activation during hemostasis. Recent studies have shown that P2X1 receptors contribute to the formation of platelet thrombi, particularly under conditions of high shear stress. Based on intracellular Ca2+ measurements a previous report has suggested that a splice variant of the P2X1 receptor, P2X1del, is expressed in platelets and, in contrast to the full-length P2X1WT receptor, is activated by ADP. In the present study we show that the P2X1del receptor fails to form functional ion channels and is below the limit of detection in human platelets. Furthermore, ADP does not contribute to the rapid ionotropic P2X receptor-mediated response in platelets. These results support the notion that ATP is the principal physiologic agonist at P2X1 receptors and that it plays a role in the activation of platelets.
通过P2受体起作用的嘌呤核苷酸在血小板信号传导中起关键作用。P2X1受体是一种三磷酸腺苷（ATP）门控离子通道，介导快速的钙内流信号，但也可与随后的二磷酸腺苷（ADP）诱发的P2Y1受体介导的反应协同作用，因此可能在止血过程中促进血小板活化。最近的研究表明，P2X1受体有助于血小板血栓的形成，特别是在高剪切应力条件下。基于细胞内Ca2+测量，先前的一份报告表明，P2X1受体的一个剪接变体P2X1del在血小板中表达，并且与全长P2X1WT受体相反，它被ADP激活。在本研究中，我们表明P2X1del受体无法形成功能性离子通道，并且在人血小板中低于检测限。此外，ADP对血小板中快速离子型P2X受体介导的反应没有贡献。这些结果支持以下观点：ATP是P2X1受体的主要生理激动剂，并且它在血小板活化中起作用。
