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 AA861, a selective inhibitor of 5-lipoxygenase, dose dependently inhibited acetylcholine release from the myenteric plexus of guinea-pig ileum induced by electrical field stimulation. Metabolites of arachidonic acid produced by the 5-lipoxygenase pathway, such as 5-hydroxyeicosatetraenoic acid (5-HETE), leukotriene C4, D4 and E4, reversed the inhibitory effect of AA861. Among them, leukotriene D4 was the most potent, having an EC50 value of about 3 nM. The present study shows for the first time that 5-lipoxygenase metabolites may have a modulatory effect on acetylcholine release in the myenteric plexus of guinea-pig ileum.
Yoshikawa
S
S
Department of Veterinary Pharmacology, Osaka Prefectural University, Sakai, Japan.
Fukunaga
Y
Y
Takeuchi
T
T
Nishio
H
H
Hata
F
F
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000294:innervation*; D017998:Leukotriene D4 / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D016227:Benzoquinones; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D017998:Leukotriene D4; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D000109:Acetylcholine