Pharmacological characterization of the human P2Y11 receptor
Pharmacological characterization of the human P2Y11 receptor
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DOI：
10.1038/sj.bjp.0702909
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发表时间：
1999-11-01
影响因子：
7.3
通讯作者：
Boeynaems, JM
中科院分区：
文献类型：
--
作者：
Communi, D;Robaye, B;Boeynaems, JM
1人P2 Y（11）受体与磷酸肌醇和环AMP途径偶联。在两种不同细胞系中稳定表达后，对重组人P2 Y（11）受体进行了药理学表征：1321 N1星形细胞瘤细胞用于三磷酸肌醇测定，CHO-K1细胞用于环AMP测定。一系列核苷酸对两条途径的作用大小顺序基本一致：ATP γ S近似于BzATP > dATP > ATP > ADP β S > 2 MeATP。2 ADP β S、AMP α S和A3 P5 PS是人P2 Y（11）受体的部分激动剂。在高浓度下，这三种核苷酸能够部分抑制ATP反应。3苏拉明是比活性蓝2更有效的拮抗剂，而吡哆醛磷酸-6-偶氮苯基-2 '，4'-二磺酸完全无活性。证明P2 Y（11）受体以竞争性方式对苏拉明敏感，表观Ki值为0.82 +/- 0.07 μ M。4 ATP衍生物AR-C67085（2-丙硫基-β，γ-二氯亚甲基-D-ATP）是ADP诱导的血小板聚集的有效抑制剂，是P2 Y（11）受体最有效的激动剂，5重组人P2 Y（11）受体的药理学特征与最近在HL-60细胞中描述的环AMP偶联Pt受体的药理学特征非常相似，这表明它是相同的受体。
1 The human P2Y(11) receptor is coupled to both the phosphoinositide and the cyclic AMP pathways. A pharmacological characterization of the recombinant human P2Y(11) receptor has been conducted following stable expression in two different cell lines: the 1321N1 astrocytoma cells for inositol trisphosphate measurements and the CHO-K1 cells for cyclic AMP assays. The rank order of potency of a series of nucleotides was almost identical for the two pathways: ATP gamma S approximate to BzATP > dATP > ATP > ADP beta S > 2MeSATP.2 ADP beta S, AMP alpha S and A3P5PS behaved as partial agonists of the human P2Y(11) receptor. At high concentrations, these three nucleotides were able to partially inhibit the ATP response.3 Suramin was a more potent antagonist than reactive blue 2, whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid was completely inactive. The P2Y(11) receptor proved to be sensitive to suramin in a competitive way with an apparent K-i value of 0.82 +/- 0.07 mu M.4 The ATP derivative AR-C67085 (2-propylthio-beta, gamma-dichloromethylene-D-ATP), a potent inhibitor of ADP-induced platelet aggregation, was the most potent agonist of the P2Y(11) receptor, among the various nucleotides tested.5 The pharmacological profile of the recombinant human P2Y(11) receptor is closely similar to that of the cyclic AMP-coupled Pt receptor recently described in HL-60 cells, suggesting that it is the same receptor.