Possible involvement of a product of the 5-lipoxygenase pathway in mediation of indomethacin-induced inhibition of cholinergic transmission in guinea-pig ileum.
Indomethacin inhibited the contractile response of longitudinal muscle of guinea-pig ileum to field stimulation in a concentration-dependent manner. The indomethacin-induced inhibition of field stimulation was mainly presynaptic because indomethacin inhibited 3H-release from the preparation preloaded with [3H]choline, but not the acetylcholine-induced contraction. FPL-55712 (1 microM) neutralized the indomethacin-induced inhibition. Arachidonic acid (1 microM), leukotriene C4 (10 nM) and prostaglandin E2 (10 nM) augmented the contractile response to field stimulation. However, 5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE, 10 microM) slightly inhibited the contractile response to field stimulation, and the inhibition was neutralized by FPL-55712. In the presence of indomethacin, [14C]arachidonic acid was metabolized into an unknown substance which had a slightly smaller Rf value than did arachidonic acid. The present results suggest that the indomethacin-induced inhibitory effect on the contractile response to field stimulation could be due to some arachidonic acid metabolites in addition to prostaglandin depletion.
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D015232:Dinoprostone; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D001095:Arachidonic Acids; D002867:Chromones; D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; D013189:SRS-A; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C006312:FPL 55712; D008084:Lipoxygenase; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin