Primary and secondary agonists can use P2X(1) receptors as a major pathway to increase intracellular Ca(2+) in the human platelet.
Primary and secondary agonists can use P2X(1) receptors as a major pathway to increase intracellular Ca(2+) in the human platelet.
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DOI：
10.1111/j.1538-7836.2007.02525.x
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发表时间：
2007-05
期刊：
影响因子：
--
通讯作者：
Mahaut-Smith MP
中科院分区：
文献类型：
--
作者：
Fung CY;Cendana C;Farndale RW;Mahaut-Smith MP
这就是Nurden。ATP是否通过P2 X1受体调节血小板活化和血栓形成？第907-9页在血小板中，许多G蛋白和酪氨酸激酶偶联受体刺激磷脂酶C依赖性Ca 2+动员已得到证实;然而，腺苷5′-三磷酸（ATP）门控P2 X1受体的二次激活在多大程度上有助于细胞内Ca 2+反应仍不清楚。我们现在发现，选择性抑制P2 X1受体可显著降低人血小板中几种重要激动剂引起的[Ca 2 +]i增加;对于胶原蛋白、血栓素A2、凝血酶和5′-二磷酸腺苷（ADP），最大效应分别降低至对照组的18%、34%、52%和69%。P2 X1对二次Ca ~（2+）反应的直接贡献远远大于由共同释放的ADP激活的P2 Y受体或通过协同P2 X1：P2 Y相互作用激活的P2 Y受体。P2 X1对峰值Ca 2+增加的相对贡献随初始刺激的强度而变化，对于糖蛋白VI和PAR-1，低水平刺激比高水平刺激更大，而P2 X1在低水平和高水平刺激血栓烷A2受体时贡献相等。相比之下，只有强烈刺激P2 Y受体导致显着的P2 X1受体激活。ATP释放检测可溶性β-内酰胺酶：荧光素酶在所有激动剂刺激二级P2 X1受体激活。然而，P2 X1受体的刺激更早，并在更大程度上比预测的平均ATP释放，这可以占主导地位的自分泌机制的激活。鉴于[Ca 2 +]i增加在血小板活化中的核心作用，这些研究表明，ATP应与ADP和血栓素A2一起被视为重要的二级血小板激动剂。
See also Nurden AT. Does ATP act through P2X1 receptors to regulate platelet activation and thrombus formation? This issue, pp 907–9. In the platelet, it is well established that many G-protein- and tyrosine kinase-coupled receptors stimulate phospholipase-C-dependent Ca2+ mobilization; however, the extent to which secondary activation of adenosine 5′-triphosphate (ATP)-gated P2X1 receptors contributes to intracellular Ca2+ responses remains unclear. We now show that selective inhibition of P2X1 receptors substantially reduces the [Ca2+]i increase evoked by several important agonists in human platelets; for collagen, thromboxane A2, thrombin, and adenosine 5′-diphoshate (ADP) the maximal effect was a reduction to 18%, 34%, 52%, and 69% of control, respectively. The direct contribution of P2X1 to the secondary Ca2+ response was far greater than that of either P2Y receptors activated by co-released ADP, or via synergistic P2X1:P2Y interactions. The relative contribution of P2X1 to the peak Ca2+ increase varied with the strength of the initial stimulus, being greater at low compared to high levels of stimulation for both glycoprotein VI and PAR-1, whereas P2X1 contributed equally at both low and high levels of stimulation of thromboxane A2 receptors. In contrast, only strong stimulation of P2Y receptors resulted in significant P2X1 receptor activation. ATP release was detected by soluble luciferin:luciferase in response to all agonists that stimulated secondary P2X1 receptor activation. However, P2X1 receptors were stimulated earlier and to a greater extent than predicted from the average ATP release, which can be accounted for by a predominantly autocrine mechanism of activation. Given the central role of [Ca2+]i increases in platelet activation, these studies indicate that ATP should be considered alongside ADP and thromboxane A2 as a significant secondary platelet agonist.
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影响因子：
20.3
作者：
Tolhurst, G;Vial, C;Mahaut-Smith, MP
通讯作者：
Mahaut-Smith, MP
影响因子：
4.1
作者：
MORTON, LF;HARGREAVES, PG;BARNES, MJ
通讯作者：
BARNES, MJ
影响因子：
10.4
作者：
Jackson, SP;Nesbitt, WS;Kulkarni, S
通讯作者：
Kulkarni, S
影响因子：
6.7
作者：
Fung, CYE;Brearley, CA;Mahaut-Smith, MR
通讯作者：
Mahaut-Smith, MR
DOI：
10.1006/bbrc.2001.4816
发表时间：
2001-05-04
影响因子：
3.1
作者：
Savi, P;Labouret, C;Herbert, JM
通讯作者：
Herbert, JM