PURINOCEPTORS ON BLOOD-PLATELETS - FURTHER PHARMACOLOGICAL AND CLINICAL-EVIDENCE TO SUGGEST THE PRESENCE OF 2 ADP RECEPTORS
PURINOCEPTORS ON BLOOD-PLATELETS - FURTHER PHARMACOLOGICAL AND CLINICAL-EVIDENCE TO SUGGEST THE PRESENCE OF 2 ADP RECEPTORS
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DOI：
10.1111/j.1365-2141.1995.tb05319.x
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发表时间：
1995-10-01
影响因子：
6.5
通讯作者：
CAZENAVE, JP
中科院分区：
文献类型：
--
作者：
GACHET, C;CATTANEO, M;CAZENAVE, JP
ADP引起的血小板聚集在动脉血栓形成的发展和扩展中起重要作用。抗血栓的噻吩吡啶化合物噻氯匹定和氯吡格雷已被证明是研究adp诱导的血小板活化机制的有用工具。从本质上讲，尽管氯吡格雷已被证明可以完全和选择性地阻断adp诱导的血小板聚集、G蛋白活化和腺苷酸环化酶的抑制，但这种药物不影响形状改变和Ca2+内流。使用非水解配体[P-33]2MeSADP的结合研究表明，人类血小板含有约600个2MeSADP的高亲和力结合位点（K-d约为5 nM）。这些位点呈现PLT受体的药理学特征。氯吡格雷治疗使大鼠血小板上的位点数量减少了70%（从1200个减少到450个），并使剩余的结合位点对氯吡格雷产生抗性。此外，先天性adp诱导的血小板聚集缺陷但正常形状改变的患者显示出非常低水平的[P-33]2MeSADP结合位点。因此，目前的数据强烈表明存在两种ADP受体，一种负责形状变化和快速Ca2+内流，另一种是Gi蛋白偶联受体，负责从内部储存中动员Ca2+，抑制腺苷酸环化酶和血小板聚集。
Platelet aggregation by ADP plays a major role in the development and extension of arterial thrombosis. The antithrombotic thienopyridine compounds ticlopidine and clopidogrel have proved useful tools to investigate the mechanisms of ADP-induced platelet activation. In essence, although clopidogrel has been shown to completely and selectively block ADP-induced platelet aggregation, G protein activation and inhibition of adenylyl cyclase, this drug does not affect shape change and Ca2+ influx. Binding studies, using the non-hydrolysable ligand [P-33]2MeSADP, have shown that human platelets contain about 600 high-affinity binding sites for 2MeSADP (K-d approximate to 5 nM). These sites present pharmacological characteristics of a PLT receptor. Clopidogrel treatment reduces the number of sites by 70% on rat platelets (from 1200 to 450) and leaves the residual binding sites resistant to clopidogrel, Moreover, patients with congenital impairment of ADP-induced platelet aggregation but normal shape change display very low levels of [P-33]2MeSADP binding sites. he current data thus strongly suggest the presence of two ADP receptors, one responsible for shape change and rapid Ca2+ influx and the other a Gi protein-coupled receptor responsible for Ca2+ mobilization from internal stores, inhibition of adenylyl cyclase and platelet aggregation.