Rolf Michael G, Mahaut-Smith Martyn P
Department of Physiology, University of Cambridge, UK.
Thromb Haemost. 2002 Sep;88(3):495-502.
G-protein-coupled P2Y1 and P2Y12 receptors play key roles in platelet activation, however the importance of ionotropic P2X1 receptors remains unclear. Platelet P2X1 responses are highly labile in vitro, but were greatly enhanced by increasing [Ca2+]o in the range 1-10 mM. The P2X1 agonist alpha,beta-MeATP stimulated a shape change which saturated at peak [Ca2+]i of > or = 400 nM, without evidence for aggregation. The maximal P2X1-evoked transmission decrease was 82% of that obtained via P2Y1 receptors. alpha,beta-MeATP caused a disc to sphere transformation in virtually all platelets, but lacked the long processes produced by ADP. Following block of P2Y1 receptors with A3P5PS, co-stimulation with alpha,beta,-MeATP and ADP failed to induce aggregation despite the generation of peak [Ca2+]i responses similar to those stimulated via P2Y1 receptors. Therefore early, transient Ca2+ influx via P2X1 receptors can contribute to platelet activation by stimulating a significant morphological change, but does not readily synergise with P2Y12 receptors to support aggregation.
G蛋白偶联的P2Y1和P2Y12受体在血小板激活中起关键作用，然而离子型P2X1受体的重要性仍不清楚。血小板P2X1反应在体外高度不稳定，但在1-10 mM范围内增加细胞外钙离子浓度（[Ca2+]o）时会大大增强。P2X1激动剂α,β-亚甲基ATP（alpha,beta-MeATP）刺激了一种形状变化，在细胞内钙离子峰值浓度（[Ca2+]i）≥400 nM时达到饱和，且无聚集迹象。P2X1引发的最大传递减少量是通过P2Y1受体获得的最大传递减少量的82%。α,β-亚甲基ATP几乎使所有血小板发生盘状到球状的转变，但没有ADP产生的长突起。在用A3P5PS阻断P2Y1受体后，尽管产生的细胞内钙离子峰值反应与通过P2Y1受体刺激产生的反应相似，但α,β-亚甲基ATP和ADP共同刺激未能诱导聚集。因此，早期通过P2X1受体的短暂钙离子内流可通过刺激显著的形态变化促进血小板激活，但不易与P2Y12受体协同支持聚集。
