title: Orexin A affects ascending contraction depending on downstream cholinergic neurons and descending relaxation through independent pathways in mouse jejunum.
abstract: The involvement of orexin in neural pathways for peristalsis was examined in mouse jejunal segments. Localized distension of the segments using a small balloon resulted in ascending contraction and descending relaxation. Ascending contraction was abolished by atropine and tetrodotoxin. Desensitization to orexin A (OXA) and SB-334867-A, an orexin-1 receptor antagonist, significantly inhibited ascending contraction. Hexamethonium also produced a significant inhibition. Exogenous administration of either OXA or nicotine induced a transient contraction that was completely inhibited by atropine and tetrodotoxin. The OXA-induced contraction was significantly inhibited by hexamethonium and SB-334867-A, whereas the nicotine-induced contraction was not inhibited by SB-334867-A. Descending relaxation was either partially or completely inhibited by l-nitroarginine and tetrodotoxin, respectively. Both SB-334867-A and hexamethonium partially inhibited descending relaxation. A combination of SB-334867-A and hexamethonium had an additive inhibitory effect on descending relaxation. Exogenous OXA, in the presence of atropine, induced a relaxation that was significantly inhibited by both l-nitroarginine and SB-334867-A, but not by hexamethonium. Nicotine in the presence of atropine relaxed the jejunal segment. SB-334867-A, unlike hexamethonium, did not affect nicotine-induced relaxation. These results suggest that OXA plays an important role in the ascending and descending neural reflexes in the mouse jejunum.
authors.affiliation: Department of Veterinary Pharmacology, Graduate school of Life and Environmental Sciences, Osaka Prefecture University, Gakuen-cho 1-1, Sakai 599-9531, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Satoh
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okishio
authors.forename: Yasu-Taka
authors.initials: YT
authors.lastname: Azuma
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakajima
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Hata
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001583:Benzoxazoles / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009287:Naphthyridines; D009434:Neural Pathways / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D000068797:Orexins; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D018733:Nicotinic Antagonists; D000068797:Orexins; D019335:Nitroarginine; D018738:Hexamethonium; D014508:Urea; D001120:Arginine; D000109:Acetylcholine