Abstract
Present study was designed to characterize the postjunctional muscarinic acetylcholine receptor mediating contraction of the chicken proventriculus by using muscarinic receptor agonists and antagonists. Muscarinic agonists caused concentration-dependent contraction. The ranking order of pEC50 values were muscarine > arecaidine propargyl ester > oxotremorine M > carbachol > methacholine > arecoline > acetylcholine > bethanechol = McN-A343 = pilocarpine. The responses to carbachol were competitively antagonized by AF-DX116 (pKb =5.9), AF-DX384 (6.84), 4-DAMP (8.79), methoctramine (5.81), pirenzepine (6.78), p-F-HHSID (7.41), atropine (8.43),tropicamide (6.91), himbacine (7.01), AQ-RA741 (6.6) and dimethindene (6.73). The correlation of pKb of the chicken proventriculus with that of the mammalian M3 receptor was the highest among five muscarinic receptors. The proventriculus membrane contained a single class of [3 H]-quinuclidinyl benzilate binding sites. pKi values of the antagonists in a binding displacement study correlated with that of the M3 subtype. Pertussis toxin(100µg/kg, i.p. for 72h) significantly decreased the contraction induced by a low concentration of carbachol. In 4-DAMP mustard and AF-DX116-pretreated muscle strips, AF-DX116 shifted the concentration-response curve for oxotremorine M to the right in the presence of 5-hydroxytryptamine and forskolin. The pKb value (6.22) was significantly higher than that obtained in the normal condition (5.78). Isoproterenol increased cyclic AMP, and carbachol significantly decreased the isoproterenol-induced increase in cyclic AMP. The results indicated that a muscarinic agonist mainly acts on the M3 receptor to cause contraction of the chicken proventriculus but the possible involvement of M2 /M4 receptors cannot be excluded as demonstrated in mammalian gastrointestinal tract.
Citation
Kitazawa T, Kondo N and Taneike T. Pharmacological Characterization of Muscarinic Receptor Subtypes Involved in Carbachol-Induced Contraction of the Chicken Proventriculus. J Gastroenterol. 2016; 2(1): 1003.