Role of P2Y1 purinoceptor in ADP-induced platelet activation
Role of P2Y1 purinoceptor in ADP-induced platelet activation
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DOI：
10.1016/s0014-5793(98)00025-8
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发表时间：
1998-02-06
期刊：
影响因子：
3.5
通讯作者：
Herbert, JM
中科院分区：
文献类型：
--
作者：
Savi, P;Beauverger, P;Herbert, JM
ADP通过其特异性受体激动血小板聚集，其作用尚待鉴定。通过PCR扩增人血小板cDNA文库证实了血小板中存在P2 Y1受体mRNA。为了确定这些P2 Y1受体是否仅参与ADP诱导的血小板活化，我们测定了P2 Y1受体拮抗剂A3 P5 PS的作用，我们发现A3 P5 PS取代了约27%的[P-33]2-MeS-ADP结合，[P-33]2-MeS-ADP是一种对氯吡格雷（一种选择性抗ADP剂）治疗有抗性的受体群体，A3 P5 PS特异性地抑制2-MeS-ADP诱导的形状改变和钙增加，但不影响腺苷酸环化酶的下调，2-MeS-ADP诱导的血小板聚集也被A3 P5 PS抑制，但当血小板被非聚集性化合物5-羟色胺进一步激活时，因此表明P2 Y1介导的刺激是ADP诱导血小板聚集的绝对先决条件，并且是血小板活化和聚集发生的关键事件。因此这些结果表明ADP诱导的聚集不能单独归因于P2 Y1的活化，但必须归因于高亲和力受体（P2 Y1）和ADP的低亲和力受体（仍待发现）的同时激活，它们中的每一个都是必需的，但都不能单独触发聚集。(C)1998年欧洲生物化学学会联合会。
ADP acts as an agonist of platelet aggregation via specific receptors which are still to be characterised, Amplification by PCR of a human platelet cDNA library confirmed the presence of mRNA of the P2Y1 receptor in platelets, In order to determine if these P2Y1 receptors mere involved in ADP-induced platelet activation, me determined the effects of A3P5PS, an antagonist of the P2Y1 receptor, on the binding of [P-33]2-MeS-ADP, a potent analogue of ADP, We found that A3P5PS displaced about 27% of [P-33]2-MeS-ADP binding, a receptor population which has been shown to be resistant to treatment with clopidogrel, a selective anti-ADP agent, A3P5PS specifically inhibited 2-MeS-ADP-induced shape change and calcium increase but did not affect adenylyl cyclase down-regulation, 2-MeS-ADP-induced platelet aggregation was also inhibited by A3P5PS but was restored when platelets were further activated by serotonin, a non-aggregating compound, therefore suggesting that P2Y1-mediated stimulation is an absolute prerequisite for ADP to induce platelet aggregation and a key event for platelet activation and aggregation to occur, These results therefore show that ADP-induced aggregation cannot be attributed to activation of P2Y1 alone, but must be attributed to the simultaneous activation of the high affinity receptor (P2Y1) and a low affinity receptor of ADP (still to be discovered), each of them essential, but neither able to trigger aggregation alone. (C) 1998 Federation of European Biochemical Societies.