SM Journal of Gastroenterology & Hepatology

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Pharmacological Characterization of Muscarinic Receptor Subtypes Involved in Carbachol-Induced Contraction of the Chicken Proventriculus

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.

Takio Kitazawa¹*, Nahoko Kondo¹ and Tetsuro Taneike¹


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A Case Report on Ulcerative Colitis with Interventional Outcomes

Ulcerative Colitis (UC) is a mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon. Main causes are gut microbiota, dysregulation of the host’s immune system, genetic susceptibility and environmental factors. Active disease can be associated with a rise in acute phase reactants [C - reactive protein (CRP)], platelet count and Erythrocyte Sedimentation Rate (ESR) and a decrease in hemoglobin. Colonoscopy is used to assess disease activity and is often performed before treatment. In this case, recurrence UC was observed and it was treated with suitable therapy but some drug interactions like metronidizole additive effect with ofloxacin results in ST-T elevation and adverse effects like abdominal pain, burning pain in midsternal area radiating to epigastric region [Calcium+Vitamin-D] were seen. Those are monitored by the alternative therapy like dose management and drug alterations.

Sandeep RJ¹, Hari HC², Jyothsna RD² and Mahender V²*