Introduction of alkynyl chains on C-8 of adenosine led to very selective antagonists of the A(3) adenosine receptor

Some 8-alkynyladenosines were synthesized and evaluated for their adenosine receptor activity, utilizing radioligand binding studies (A(1), A(2A), A(3 )) or adenylyl cyclase activity assays (A(2B)). Furthermore, the maximal in duction of guanosine 5 '-(gamma -thio)triphosphate ([S-35]GTP gammaS) bindi ng to G proteins and the inhibition of NECA-stimulated binding, in membrane s of CHO cells which express the human A(3) receptor, were used to determin e the intrinsic activity of these nucleosides at the A(3) adenosine recepto r. The results showed that these new adenosine derivatives are very selecti ve ligands for the A(3) receptor subtype and behave as adenosine antagonist s, since they do not stimulate basal [S-35]GTP gammaS binding, but inhibit NECA-stimulated binding. This is the first report that adenosine derivative s, with unmodified ribose moiety, are adenosine receptor antagonists. (C) 2 001 Elsevier Science Ltd. All rights reserved.