Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum.
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.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001583:Benzoxazoles / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017615:Enteric Nervous System / Q000187:drug effects; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009287:Naphthyridines; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D010275:Parasympathetic Nervous System / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D002352:Carrier Proteins; D005730:Ganglionic Blockers; D047908:Intracellular Signaling Peptides and Proteins; D018727:Muscarinic Antagonists; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D018738:Hexamethonium; D013779:Tetrodotoxin; D001285:Atropine; D014508:Urea; D000109:Acetylcholine