P2Y12, a new platelet ADP receptor, target of clopidogrel
P2Y12, a new platelet ADP receptor, target of clopidogrel
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DOI：
10.1006/bbrc.2001.4816
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发表时间：
2001-05-04
影响因子：
3.1
通讯作者：
Herbert, JM
中科院分区：
文献类型：
--
作者：
Savi, P;Labouret, C;Herbert, JM
在转染人P2 Y（12）受体的CHO细胞上测定了ADP类似物P-33- 2 MeS-ADP的结合特性。这些转染的CHO细胞显示出对P-33- 2 MeS-ADP的强亲和力，其结合特性在所有点上与在血小板上观察到的那些相对应。特别地，该受体识别具有以下效力顺序的嘌呤：2 MeS-ADP = 2 MeS-ATP> ADP = ATP γ S = ATP >> UTP，结合特征与血小板中获得的结合特征相似。pCMPS可拮抗~（33）P-2 MeS-ADP的结合，而P_2Y（1）和aggregin的拮抗剂MRS 2179和FSBA则不拮抗~（33）P-2 MeS-ADP的结合。此外，P-33- 2 MeS-ADP与这些细胞的结合被氯吡格雷的活性代谢物强烈且不可逆地抑制，其效力与该化合物在血小板上观察到的效力一致。与血小板一样，2 MeS-ADP在这些P2 Y（12）转染的CHO细胞中诱导腺苷酸环化酶下调，而在相应的未转染细胞中不存在这种效应。如在血小板中所示，氯吡格雷的活性代谢产物拮抗2 MeS-ADP诱导的转染细胞上腺苷酸环化酶的抑制。我们的结果证实P2 Y（12）是以前称为“血小板P2 t（AC）”受体，并表明该受体被氯吡格雷的活性代谢物拮抗。(C)北京：科学出版社.
The binding characteristics of P-33-2MeS-ADP, a stable analogue of ADP, were determined on CHO cells transfected with the human P2Y(12) receptor, a novel purinergic receptor. These transfected CHO cells displayed a strong affinity for P-33-2MeS-ADP, the binding characteristics of which corresponded in all points to those observed on platelets. In particular, this receptor recognised purines with the following order of potency: 2MeS-ADP = 2MeS-ATP > ADP = ATP gammaS = ATP >> UTP, a binding profile which is similar to that obtained in platelets. The binding of 33P-2MeS-ADP was antagonised by pCMPS but not by MRS2179 and FSBA, antagonists of P2Y(1) and aggregin, respectively. Moreover, the binding of P-33-2MeS-ADP to these cells was strongly and irreversibly inhibited by the active metabolite of clopidogrel with a potency which was consistent with that observed for this compound on platelets. Like in platelets, 2MeS-ADP induced adenylyl cyclase down-regulation in these P2Y(12) transfected CHO cells, an effect which was absent in the corresponding non-transfected cells. As already shown in platelets, the active metabolite of clopidogrel antagonised 2MeS-ADP-induced inhibition of adenylyl cyclase on transfected cells. Our results confirm that P2Y(12) is the previously called "platelet P2t(AC)" receptor and show that this receptor is antagonised by the active metabolite of clopidogrel. (C) 2001 Academic Press.