Pharmacological characterization of 5-hydroxytryptamine-induced contraction in the chicken gastrointestinal tract.
5-Hydroxytryptamine (5-HT) receptor subtypes involved in 5-HT-induced contraction of the chicken gastrointestinal tract were characterized pharmacologically using subtype-selective agonists and antagonists. The proventriculus (area of stomach adjacent to the oesophagus) and ileum are examined. 5-HT applied cumulatively caused sustained contraction of the proventriculus that was not decreased by tetrodotoxin, atropine or l-nitro-arginine methylester (l-NAME). alpha-Methyl-5-HT showed the same potency as that of 5-HT, indicating the involvement of the 5-HT(2) receptor. (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI), 5-methoxytryptamine and 1-(3-chlorophenyl)piperazine hydrochloride (mCPP) were potent, and 2-methyl-5-HT, 5-carboxamidotryptamine, BW723C86 and 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK212) were moderate, but (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT), [endo-N-8-methyl-8-azabicyclo-(3,2,1)oct-3-yl]-2,3-dihydro-(1-methyl)ethyl-2-oxo-1H-benzimidazol-1-carboxamide (BIMU-8) and cisapride were weak agonists. Correlation of pEC(50) values of these agonists with documented pEC(50) values for 5-HT(2C) receptor was higher than 5-HT(2A) and 5-HT(2B). Cinanserin, ketanserin, methiothepin, methysergide, mianserin, (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl)-1,3,8-triazaspiro[4,5]decane-2,4-dione hydrochloride (RS102221), N-(1-methyl-1H-indolyl-5-yl)-N'-(3-methyl-5-isothiazolyl)urea (SB204741), spiperone and N-desmethylclozapine concentration-dependently inhibited the contractile responses to 5-HT. Correlation of pK(b)/pA(2) of antagonists with documented pK(i) for 5-HT(2C) receptor was highest among 5-HT(2) receptor subtypes. In the methysergide- and ketanserin-treated proventriculus, 5-HT, 2-methyl-5-HT and cisapride did not enhance the electrical field stimulation (5 Hz)-induced cholinergic contractions. 5-HT applied non-cumulatively caused transient contraction of ileum, and the responses were partly decreased by atropine or tetrodotoxin. 5-Methoxytryptamine, alpha-methyl-5-HT, 5-carboxamidotryptamine, L692,247 and DOI were potent agonists. However, 2-methyl-5-HT, cisapride, BW723C86, 8-OH-DPAT and 5-nonyloxytryptamine, mCPP and MK212 were less effective. Ketanserin and methysergide decreased the 5-HT-induced ileal contraction, but neither GR113808 nor SB269970 inhibited the responses. In conclusion, 5-HT causes contraction of the proventriculus via 5-HT(2C)-like receptors present on smooth muscle. 5-HT also causes contraction of the ileum, but the underlying mechanisms are complex, involving neural and smooth muscle components, and both 5-HT(1)- and 5-HT(2)-like receptors. Neural 5-HT receptors similar to 5-HT(3)/5-HT(4) receptors were not found in the chicken proventriculus and ileum.
Department of Pharmacology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
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Kitazawa
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Ukai
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Komori
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Taneike
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002645:Chickens / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007082:Ileum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D011531:Proventriculus / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000187:drug effects* / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin; D018490:Serotonin Agents / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000779:Anesthetics, Local; D018727:Muscarinic Antagonists; D044346:Receptor, Serotonin, 5-HT1D; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D018490:Serotonin Agents; D013141:Spiro Compounds; D013449:Sulfonamides; D012701:Serotonin; D013779:Tetrodotoxin; D001285:Atropine; D007650:Ketanserin