Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum |
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Authors: | Matsuo Katsuhisa Kaibara Muneshige Uezono Yasuhito Hayashi Hideki Taniyama Kohtaro Nakane Yoshibumi |
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Institution: | Department of Psychiatry, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan. |
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Abstract: | The mechanism underlying orexin-induced contraction was examined in isolated preparations of guinea pig ileum, in relation to cholinergic transmission. Orexin-A caused contraction of ileal strips in a concentration-dependent manner. 1-(2-Methylbenzoxazol-6-yl)-3-1,5]napthyridin-4-yl-urea hydrochloride (SB-334867-A) antagonized the orexin-A-induced contraction, with no effects on the acetylcholine-induced contraction and twitch contractions. The orexin-A-induced contraction was inhibited by tetrodotoxin and atropine, but not by hexamethonium, an antagonist of vasoactive intestinal peptide and a mixture of 5-hydroxytryptamine receptor antagonists. Orexin-A evoked an outflow of 3H]acetylcholine from the ileal strips preincubated with 3H]choline, in a concentration-dependent manner, and the orexin-A-evoked outflow was inhibited by tetrodotoxin, indicating that the outflow of 3H]acetylcholine originates from the nerve terminals. The orexin-A-evoked outflow of 3H]acetylcholine was antagonized by SB-334867-A. Thus, orexin-A evokes the release of acetylcholine from the enteric cholinergic neurons due to stimulation of the orexin-1 receptors and then causes contractions of guinea pig ileum. |
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Keywords: | Orexin-A Orexin-1 receptor SB-334867-A Acetylcholine release Tetrodotoxin |
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