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Kitazawa T, Ukai H, Komori S, Taneike T: Pharmacological characterization of 5-hydroxytryptamine-induced contraction in the chicken gastrointestinal tract. Auton Autacoid Pharmacol. 2006 Apr;26(2):157-68.
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-oxope ntyl)-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. |
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