Diverse inhibitors of intracellular signalling act as adenosine receptor antagonists

被引:27
作者
Schulte, G [1 ]
Fredholm, BB [1 ]
机构
[1] Karolinska Inst, Dept Physiol & Pharmacol, Sect Mol Neuropharmacol, S-17177 Stockholm, Sweden
关键词
kinase inhibitor; adenylyl cyclase inhibitor; adenosine receptor; antagonist;
D O I
10.1016/S0898-6568(01)00228-5
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Inhibitors of intracellular signalling events, including enzyme inhibitors, are often used to investigate signal transduction pathways. We examined whether some inhibitors that act on the ATP site of enzymes are also potent adenosine receptor antagonists. Competitive radioligand binding assays in membranes or brain sections show that genistein, chelerythrine, and SQ22536 [9-(tetrahydro-2'-furyl) adenine] block A(1,) A(2A), and A(3) adenosine receptors in concentrations of these drugs commonly used to examine cellular signalling (K-1 of [H-3]-DPCPX (1,3-diproyl-8-cyclopentylxanthine) competition mean (95% confidence interval): 2.6 (1.5-4.8) muM, 5.7 (2.1-15.8) muM, 59.4 (17.3-203.8) muM; K-1 of [H-3]-SCH58261 [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine] competition: 15.3 (8.1-28.8) muM, 37.6 (10.3-137.4) muM, 16.7 (11.5-24.3) muM for genistein, chelerthine, and SQ22536,respectively). Given that adenosine receptors are present on most cells, that adenosine is often present, and that adenosine receptors interact functionally with several signalling pathways, these results may be of significance also when studying signalling via other receptors. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:109 / 113
页数:5
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