MODULATION OF ACETYLCHOLINE-RELEASE FROM THE MYENTERIC PLEXUS OF GUINEA-PIG ILEUM BY 5-LIPOXYGENASE METABOLITES OF ARACHIDONIC-ACID

Eicosatetraenoic acid, an inhibitor of 5- and 12-lipoxygenase, and AA8 61, a selective inhibitor of 5-lipoxygenase, dose dependently inhibite d acetylcholine release from the myenteric plexus of guinea-pig ileum induced by electrical field stimulation. Metabolites of arachidonic ac id produced by the 5-lipoxygenase pathway, such as 5-hydroxyeicosatetr aenoic acid (5-HETE), leukotriene C4, D4 and E4, reversed the inhibito ry effect of AA861. Among them, leukotriene D4 was the most potent, ha ving an EC50 value of about 3 nM. The present study shows for the firs t time that 5-lipoxygenase metabolites may have a modulatory effect on acetylcholine release in the myenteric plexus of guinea-pig ileum.