Orexin A affects ascending contraction depending on downstream cholinergic neurons and descending relaxation through independent pathways in mouse jejunum.
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.
Satoh
Yuji
Y
Department of Veterinary Pharmacology, Graduate school of Life and Environmental Sciences, Osaka Prefecture University, Gakuen-cho 1-1, Sakai 599-9531, Japan.
Okishio
Yutaka
Y
Azuma
Yasu-Taka
YT
Nakajima
Hidemitsu
H
Hata
Fumiaki
F
Takeuchi
Tadayoshi
T
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
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