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.
Takaki
M
M
Department of Physiology, Okayama University Medical School, Japan.
Namba
T
T
Fujii
W
W
Suga
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D008643:Mesentery / Q000294:innervation*; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D009476:Neurons, Efferent / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D013373:Substance P; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D000109:Acetylcholine; D002211:Capsaicin; D015056:1-Methyl-3-isobutylxanthine