Abstract
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.
MeSH terms
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Acetylcholine / metabolism*
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Animals
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Arachidonic Acid / metabolism
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Arachidonic Acids / pharmacology
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Benzoquinones / pharmacology
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Electric Stimulation
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Guinea Pigs
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Hydroxyeicosatetraenoic Acids / pharmacology*
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Ileum / drug effects
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Ileum / innervation*
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Leukotriene D4 / pharmacology
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Leukotrienes / pharmacology*
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Lipoxygenase Inhibitors / pharmacology*
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Male
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Myenteric Plexus / drug effects*
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Myenteric Plexus / metabolism
Substances
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Arachidonic Acids
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Benzoquinones
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Hydroxyeicosatetraenoic Acids
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Leukotrienes
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Lipoxygenase Inhibitors
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Arachidonic Acid
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5-hydroxy-6,8,11,14-eicosatetraenoic acid
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Leukotriene D4
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2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone
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Acetylcholine