Adenosine receptor activation in human fibroblasts: nucleoside agonists and antagonists.

Adenosine (ED50 15 μM) causes a 50-fold increase in intracellular cyclic AMP in the VA13 human fibroblast line. A total of 128 nucleosides was tested as agonists and antagonists. Eight classes of compounds were found: full agonists (14 compounds), weak agonists (20), high-efficacy partial agonists (16), low-efficacy partial agonists (7), competitive inhibitors (11), noncompetitive inhibitors (3), partial agonist - noncompetitive inhibitors (3), and inactive compounds (54). The noncompetitive inhibitors antagonized the responses to adenosine, isoproterenol, and prostaglandin E1 and thus may have been adenylate cyclase inhibitors. The most potent noncompetitive inhibitor, 2′,5′-dideoxyadenosine, was a partial inhibitor, reducing the response to isoproterenol by only 77% even at very high concentrations. The most potent agonists, partial agonists, and pure antagonists had apparent affinities of about 5 μM. Although all positions were important for affinity at the adenosine receptor, only the 3′- and 5′-posit...