Adenosine inhibits efferent function of extrinsic capsaicin-sensitive sensory nerves in the enteric nervous system

Capsaicin (1-3 microM) and electrical stimulation of mesenteric nerves in the presence of hexamethonium and guanethidine antidromically stimulate extrinsic sensory nerve fibers to produce a specific slow depolarizing response of myenteric neurons and a contractile response of muscles in the isolated guinea-pig ileum, mediated by release of substance P and acetylcholine. Adenosine (1-100 microM) inhibited the response to mesenteric nerve stimulation. Adenosine (10-100 microM) suppressed the contractile response to a threshold concentration of capsaicin (1 microM) while leaving the contractile response to a submaximal concentration of substance P (1 nM) and acetylcholine (0.1 microM) intact. Adenosine (1-10 microM) inhibited dose dependently the capsaicin 10 microM)-induced depolarization of myenteric neurons, but did not inhibit the depolarizing response to exogenous substance P. The adenosine P1 receptor antagonist, 8-phenyltheophylline (1-10 microM), antagonized the inhibitory effect of adenosine (1-10 microM) on the mechanical responses. We conclude that adenosine-induced prejunctional inhibition of the mechanical responses is mediated by adenosine P1 receptors.