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  • Title: Possible involvement of a product of the 5-lipoxygenase pathway in mediation of indomethacin-induced inhibition of cholinergic transmission in guinea-pig ileum.
    Author: Nakahata N, Ono T, Nakanishi H.
    Journal: Eur J Pharmacol; 1984 Sep 03; 104(1-2):133-8. PubMed ID: 6094206.
    Abstract:
    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.
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