Evaluation of reactive blue 2 derivatives as selective antagonists for P2Y receptors
Evaluation of reactive blue 2 derivatives as selective antagonists for P2Y receptors
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DOI：
10.1016/s1537-1891(03)00030-2
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发表时间：
2002-12-01
影响因子：
4
通讯作者：
Brown, CA
中科院分区：
文献类型：
--
作者：
Brown, J;Brown, CA
由于缺乏亚型选择性拮抗剂，P2Y受体的药理作用受到阻碍。然而，最近的一项研究评估了一系列与染料活性蓝2结构相关的化合物在P2X和P2Y受体上的拮抗剂选择性。研究发现，酸性蓝129、酸性蓝80、酸性蓝25和酸性紫34是最有效的P2Y受体拮抗剂[Naunyn Schmiedeberg‘s Arch]。药水。357(1998)111]。在这项研究中，我们确定了这四种药物选择性地拮抗由自然表达的牛主动脉内皮细胞(BAE)中的P2Y(1)和P2Y(2)受体介导的肌醇磷酸周转的能力。酸性蓝129、酸性蓝80和酸性紫34使P2Y(1)激动剂2-甲硫基三磷酸(2MeSATP)的量效曲线右移。酸性蓝129和酸性蓝80对P2Y(2)激动剂5‘-三磷酸尿苷(UTP)的拮抗作用也很弱。在30和100um时，酸性紫34对UTP的剂量反应无明显影响。然而，在10微米时，酸性紫34增强了UTP的反应。酸性蓝80、酸性蓝129和酸性紫34对P2Y和P2X具有选择性，但在P2Y和P2Y(2)受体之间的选择性较差，因此在P2Y受体药理学领域的应用有限。此外，与以往的报道相反，酸性蓝25不是一种对P2Y有选择性的拮抗剂。(C)2003 Elsevier Science Inc.保留所有权利。
P2Y receptor pharmacology is hampered by a lack of subtype selective antagonists. However, a recent study evaluated series of compounds, structurally related to the dye reactive blue 2, for their antagonist selectivity at P2X vs. P2Y receptors. Acid blue 129, acid blue 80, acid blue 25 and acid violet 34 were found to be the most potent of the antagonists studied, at P2Y receptors [Naunyn Schmiedeberg's Arch. Pharmacol. 357 (1998) 111]. In this study, we have determined the ability of these four agents to selectively antagonize inositol phosphate turnover mediated by P2Y(1) and P2Y(2) receptors that are natively expressed in bovine aortic endothelial (BAE) cells. Acid blue 129, acid blue 80, and acid violet 34 shifted the dose-response curve of the P2Y(1) agonist 2-methylthio adenosine trisphosphate (2MeSATP) to the right. Acid blue 129 and acid blue 80 were also very weak antagonists of the P2Y(2) agonist uridine 5'-triphosphate (UTP). At 30 and 100 muM, acid violet 34 failed to have any significant effect on the dose-response to UTP. However, at 10 muM, acid violet 34 enhanced the UTP responses. Acid blue 80, acid blue 129 and acid violet 34 are P2Y vs. P2X selective, but show poor selectivity between P2Y, and P2Y(2) receptors and are therefore of limited use in the field of P2Y receptor pharmacology. Furthermore, contrary to previous reports, acid blue 25 is not a P2Y-selective antagonist. (C) 2003 Elsevier Science Inc. All rights reserved.