A major role for P2XI receptors in the early collagen-evoked intracellular Ca2+ responses of human platelets

A major role for P2XI receptors in the early collagen-evoked intracellular Ca2+ responses of human platelets
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DOI:
10.1160/th04-11-0732
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发表时间:
2005-07-01
影响因子:
6.7
通讯作者:
Mahaut-Smith, MR
Mahaut-Smith, MR
中科院分区:
医学2区
文献类型:
--
作者:
Fung, CYE;Brearley, CA;Mahaut-Smith, MR

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据报道,在血小板中,ATP 门控 P2X(I) 受体可放大对胶原蛋白的功能反应,但早期 Ca2+ 动员事件的相对重要性尚不清楚。我们现在报道,P2X(I)受体活性的选择性脱敏导致细胞内Ca2+对各种胶原浓度(0.25-2 mu g ml(-1))的初始反应显着降低。在低胶原浓度和高胶原浓度下,峰值 [Ca2+] 的增加分别减少至对照的 8.5% 和 55%,最大增加率分别减少至对照的 12% 和 33%。在缺乏细胞外 Ca2+ 的情况下,没有观察到这种 P2X(I) 依赖性的胶原刺激 Ca2+ 反应的加速和增强。这些结果证明了 ATP 门控 Ca2+ 流入在早期胶原诱发 Ca2+ 信号中的主要作用,并且至少可以部分解释 P2X(I) 受体对动脉血栓形成的重要贡献。
In the platelet, ATP-gated P2X(I) receptors have been reported to amplify functional responses to collagen, however the relative importance of early Ca2+ mobilisation events is unknown. We now report that selective desensitisation of P2X(I) receptor activity leads to a major reduction in the initial intracellular Ca2+ responses to a wide range of collagen concentrations (0.25-2 mu g ml(-1)). Peak [Ca2+], increases were reduced to 8.5 and 55% of control, and the maximum rate of rise was reduced to 12 and 33% of control,at low and high collagen concentrations, respectively. This P2X(I)-dependent acceleration and enhancement of collagen-stimulated Ca2+ responses was not observed in the absence of extracellular Ca2+. These results demonstrate a major role for ATP-gated Ca2+ influx in the early collagen-evoked Ca2+ signals and can at least partly explain the important contribution of P2X(I) receptors to arterial thrombosis.