Role of prostacyclin in acetylcholine release from myenteric plexus of guinea-pig ileum.
The roles of metabolites of arachidonic acid in spontaneous and agonist-induced acetylcholine release from a longitudinal muscle preparation with myenteric plexus of guinea-pig ileum were studied. Indomethacin significantly decreased both spontaneous acetylcholine release and its release induced by nicotine and substance P. We had found that prostaglandin E2 (PGE2) partly reversed this inhibition. We now found that a stable prostacyclin analog, OP-41483 at 100 nM, completely reversed the inhibition of acetylcholine release by indomethacin. On the other hand, PGD2, PGF2 alpha and ONO-11113, a thromboxane A2 analog, did not have any significant effect on the inhibition by indomethacin. OP-41483 had no effect on acetylcholine release induced by nicotine or substance P in the absence of indomethacin. To confirm the modulatory role of endogenous prostaglandins on acetylcholine release, we also studied the release of 6-keto-PGF1 alpha, a metabolite of prostacyclin, and PGE2 from longitudinal muscle preparations. The preparations released appreciable amounts of 6-keto-PGF1 alpha continuously during the experiments. Indomethacin inhibited release, while nicotine did not affect it so significantly. Our results suggest that endogenous prostacyclin modulates acetylcholine release from cholinergic nerve terminals in the myenteric plexus of guinea-pig ileum.
Fukunaga
Y
Y
Department of Veterinary Pharmacology, College of Agriculture, University of Osaka Prefecture, Sakai, Japan.
Mine
Y
Y
Yoshikawa
S
S
Takeuchi
T
T
Hata
F
F
Yagasaki
O
O
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D009538:Nicotine; D011464:Epoprostenol; C035847:ataprost; D000109:Acetylcholine; D007213:Indomethacin