Adenosine receptors are coupled negatively to release of tachykinin(s) from enteric nerve endings.
Adenosine receptors capable of modulating tachykininergic transmission were characterized in functional studies using both field-stimulated and cholecystokinin octapeptide-stimulated contractile responses of atropinized guinea pig longitudinal muscle-myenteric plexus preparations. These tetrodotoxin-sensitive responses, which were mediated by release of one or more tachykinins, were inhibited by adenosine analogs in a concentration-dependent manner. The rank order of potencies of the analogs as inhibitors of the responses to cholecystokinin octapeptide was N6-cyclopentyladenosine greater than 5'-N-ethylcarboxamidoadenosine much greater than 2-phenylaminoadenosine (CV 1808). Schild analysis of the antagonism of the presynaptic inhibitory effects of 5'-N-ethylcarbocamidoadenosine and N6-cyclopentyladenosine on cholecystokinin octapeptide-stimulated responses using the A1 selective antagonists 1,3-dipropyl-8-(4-sulfophenyl)xanthine and 1,3-dipropyl-8-(cyclopentyl)xanthine yielded linear isoboles with unit slopes indicating competitive antagonism. The affinity of the antagonists for the receptor site(s) involved in inhibition of tachykininergic transmission was similar to those established previously for cholinergic transmission. The rank order of potency of adenosine analogs as inhibitors of the field-stimulated responses was such that N6-cyclopentyladenosine = 5'-ethylcarboxamidoadenosine. Reverse-phase high-performance liquid chromatography analysis performed on lysates of isolated myenteric nerve endings demonstrated the presence of substance P and neurokinin-A. Neurokinin-B was undetectable. These studies indicate that adenosine receptor(s) on myenteric nerve endings are coupled negatively to tachykinin release and that they are probably identical to those involved in the modulation of acetylcholine release.
Department of Pharmacology, University of Western Ontario, Canada.
F L
FL
Christofi
T J
TJ
McDonald
M A
MA
Cook
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism*; D009705:Nucleosides / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000032:analysis / Q000378:metabolism*; D019820:Xanthine; D014970:Xanthines / Q000494:pharmacology
D009705:Nucleosides; D011983:Receptors, Purinergic; D015320:Tachykinins; D014970:Xanthines; D019820:Xanthine; D013373:Substance P; D012844:Sincalide; D000109:Acetylcholine