Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine ligands, new tools to characterize A(3) adenosine receptors in human tumor cell lines

Increased concns. of extracellular adenosine are reached in ischemic or inflamed tissues but have also been detected inside tumoral masses. If this finding may account for an important role of adenosine in the pathogenesis of tumors remains to be detd. in view of its contradictory effects on cell survival and proliferation. In particular, adenosine was found to exert its effects on proliferation and on cell death mainly through the A3 adenosine receptor. Therefore, a complete pharmacol. characterization of the subtype and no. of the expressed A3 adenosine receptors is necessary for the elucidation of the role of adenosine via A3 receptors in a specific cell subtype. The lack of potent and selective radiolabeled A3 receptor antagonists has been, in the past, the major obstacle in the characterization of structure, function and regulation of this adenosine receptor subtype. Recently, our group has identified a series of substituted pyrazolotriazolopyrimidine derivs. as potent and selective antagonists to human A3 adenosine receptors. The most recent results obtained in this field are summarized in the present review. Furthermore, the review reports the results of the biochem. and pharmacol. characterization of A3 receptors in different human tumor cell lines and the multiple A3 receptor-sustained ways that could prime tumor development.