Characterization of pre‐ and post‐junctional adenosine receptors in guinea‐pig ileum

The receptors involved in adenosine‐induced modulation of cholinergic neuroeffector transmission in guinea‐pig ileum were explored by means of the non‐selective stable analogue, 2‐chloroadenosine and analogues with preference for A, receptors, L‐N⁶‐phenylisopropyladenosine (L‐PIA), AND A₂ receptors, 5′‐N‐ethylcarboxamideadenosine (NECA) and D‐N⁶‐phenylisopropyladenosine (D‐PIA). 2‐chloroadenosine, L‐PIA AND NECA were equipotent in inhibiting contractile responses to nerve stimulation, whereas D‐PIA exerted a similar activity only in high concentrations. The release of acetylcholine induced by nerve stimulation was inhibited to a similar degree by NECA, L‐PIA AND D‐PIA. The phosphodiesterase inhibitor, ZK 62.711, and the activator of adenylate cyclase, forskolin, enhanced the inhibitory effect of NECA, but not that of L‐PIA, on contractile responses to nerve stimulation. Only NECA inhibited contractions induced by direct muscle stimulation and ZK 62.711 enhanced this inhibition. It is concluded that adenosine inhibits the neuroeffector transmission in guinea‐pig ileum mainly by a prejunctional, cAMP‐independent, mechanism, involving A, receptors and a supplementary activation of post‐junctional A₂ receptors. In addition there may be a prejunctional inhibitory effect of high agonist concentrations, exerted via A₂ receptors and influenced by the prevailing levels of cAMP.