Inhibition of platelet function by administration of MRS2179, a P2Y1 receptor antagonist
Inhibition of platelet function by administration of MRS2179, a P2Y1 receptor antagonist
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DOI：
10.1016/s0014-2999(01)00733-6
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发表时间：
2001-02-02
影响因子：
5
通讯作者：
Gachet, C
中科院分区：
文献类型：
--
作者：
Baurand, A;Raboisson, P;Gachet, C
研究了强效P2Y(1)受体拮抗剂n -6-甲基-2'-脱氧腺苷-3',5'-二磷酸（MRS2179）在体外、离体及体内对腺苷-5'-二磷酸（ADP）诱导的血小板聚集的影响。在洗涤后的血小板悬液中，MRS2179抑制adp诱导的血小板形状改变、聚集和Ca2+升高，但对adp诱导的腺苷酸环化酶的抑制没有影响。使用新的放射性配体[P-33]MRS2179进行的结合研究表明，洗涤后的人血小板每个血小板显示134 +/- 8个结合位点，亲和力（K-d）为109 +/- 18 nM。最后，与对照组相比，静脉注射MRS2179可抑制ADP作用下大鼠血小板聚集，延长大鼠或小鼠出血时间。这些结果表明，这种有效的P2Y(1)受体拮抗剂是一种很有前途的工具，可以评估P2Y(1)受体在抗血栓治疗中的体内药理作用。(C) 2001 Elsevier Science B.V.版权所有
The effects of a potent P2Y(1) receptor antagonist, N-6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) on adenosine-5'-diphosphate (ADP)-induced platelet aggregation in vitro, ex vivo and on the bleeding time in vivo were determined. In suspensions of washed platelets, MRS2179 inhibited ADP-induced platelet shape change, aggregation and Ca2+ rise but had no effect on ADP-induced inhibition of adenylyl cyclase. Binding studies using the new radioligand [P-33]MRS2179 showed that washed human platelets displayed 134 +/- 8 binding sites per platelet with an affinity (K-d) of 109 +/- 18 nM. Finally, intravenous injection of MRS2179 resulted in inhibition of rat platelet aggregation in response to ADP and prolonged the bleeding time, in rats or mice, as compared to controls. These results suggest this potent P2Y(1) receptor antagonist to be a promising tool to evaluate the in vivo effects of pharmacologically targeting the P2Y(1) receptor with a view to antithrombotic therapy. (C) 2001 Elsevier Science B.V. All rights reserved.