UMR_S949 Inserm, Université de Strasbourg, EFS-Alsace 10, rue Spielmann, BP N°36, 67065, Strasbourg, France.
Purinergic Signal. 2012 Sep;8(3):609-19. doi: 10.1007/s11302-012-9303-x. Epub 2012 Apr 11.
The P2Y(12) receptor is a Gi-coupled ADP receptor first described in blood platelets where it plays a central role in the complex processes of activation and aggregation. Platelet granules store important amounts of ADP which are released upon stimulation by interaction of platelets with the damaged vessel wall. Therefore, the P2Y(12) receptor is a key player in primary hemostasis and in arterial thrombosis and is an established target of antithrombotic drugs like the thienopyridine compounds ticlopidine, clopidogrel, and prasugrel or the direct, reversible antagonists ticagrelor and cangrelor. Beyond the platelet physiology and pharmacology, recent studies have revealed the expression of the P2Y(12) receptor in other hematopoietic cells including leukocyte subtypes and microglia in the central nervous system as well as in vascular smooth muscle cells. These studies indicate putative roles of the P2Y(12) receptor in inflammatory states and diseases of the brain, lung, and blood vessels. The selective role of P2Y(12) among other P2 receptors as well as the possible impact of P2Y(12) targeting drugs in these processes remain to be evaluated.
P2Y(12) 受体是一种 Gi 偶联的 ADP 受体,最初在血小板中被描述,在血小板的激活和聚集的复杂过程中发挥核心作用。血小板颗粒储存着大量的 ADP,当血小板与受损的血管壁相互作用时,ADP 就会被释放出来。因此,P2Y(12) 受体是初级止血和动脉血栓形成的关键因素,也是抗血栓药物(如噻吩吡啶类化合物噻氯匹定、氯吡格雷和普拉格雷)或直接、可逆拮抗剂替卡格雷和坎格雷洛的既定靶点。除了血小板生理学和药理学之外,最近的研究还揭示了 P2Y(12) 受体在其他造血细胞中的表达,包括白细胞亚型和中枢神经系统中的小胶质细胞以及血管平滑肌细胞。这些研究表明 P2Y(12) 受体在大脑、肺和血管的炎症状态和疾病中可能发挥作用。P2Y(12) 受体在其他 P2 受体中的选择性作用以及 P2Y(12) 靶向药物在这些过程中的可能影响仍有待评估。