Effects of the allosteric modulator SCH-202676 on adenosine and P2Y receptors

被引：24

作者：

Gao, ZG ^{[1
]}

Gross, AS ^{[1
]}

Jacobson, KA ^{[1
]}

机构：

[1] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA

来源：

LIFE SCIENCES | 2004年 / 74卷 / 25期

关键词：

adenosine receptor; P2Y receptor; allosteric modulator; 7TM receptor; SCH-202676;

D O I：

10.1016/j.lfs.2003.11.014

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The G protein-coupled receptor allosteric modulator SCH-202676 (N-(2,3-diphenyl-1,2,4-thiadiazol-5-(2H)ylidene)methanamine), which affects a wide range of structurally unrelated G protein-coupled receptors, has highly divergent effects on purine receptors. SCH-202676 inhibited radioligand binding to human adenosine A,, A(2A), and A(3) receptors (IC50 = 0.5-0.8 muM) and affected dissociation kinetics, but at the human P2Y(1) nucleotide receptor it had no effect. SCH-202676 (10 muM) selectively accelerated agonist dissociation at adenosine A3 receptors and either slowed (adenosine A(1) receptors) or accelerated (adenosine A(2A) receptors) antagonist dissociation. Thus, SCH-202676 differentially modulated A(1), A(2A), and A(3) receptors as well as agonist- and antagonist-occupied receptors. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：3173 / 3180

页数：8

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