Evidence for specific adenosine receptors at cholinergic nerve endings.

1 An electrophysiological study was made to determine if adenosine and adenine nucleotides affect cholinergic nerve endings to frog skeletal muscle through relatively non-specific nucleotide receptors or through specific adenosine receptors. 2 Non-hydrolysable derivatives of adenosine triphosphate failed to alter the mean number of acetylcholine (ACh) quanta released by the nerve impulse (m) or the miniature endplate potential frequency (m.e.p.p.f) but N6-methyladenosine and 2-chloroadenosine, two adenosine analogues with an unsubstituted ribose moiety (R-site agonists), produced marked reductions in m and m.e.p.p.f. 3 In contrast, 2'-deoxyadenosine, a derivative with an unsubstituted purine ring (P-site agonist), generally produced increases in m and m.e.p.p.f, which further increased after removing the drug. Other P-site agonists such as 5'-deoxyadenosine (in the presence of theophylline) and 9-beta-D-arabinofuranosyl adenine also increased m and m.e.p.p.f. 4 The results suggest that two types of adenosine receptors may be present at cholinergic nerve endings, one type (R-site) mediating depression and the other type (P-site) producing enhancement of ACh release.