Diverse inhibitors of intracellular signalling act as adenosine receptor antagonists.

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(i) of [(3)H]-DPCPX (1,3-dipropyl-8-cyclopentylxanthine) competition mean (95% confidence interval): 2.6 (1.5-4.8) microM, 5.7 (2.1-15.8) microM, 59.4 (17.3-203.8) microM; K(i) of [(3)H]-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) microM, 37.6 (10.3-137.4) microM, 16.7 (11.5-24.3) microM for genistein, chelerythrine, 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.