{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:32:39Z","timestamp":1791073959375,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2255,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M<jats:sub>3<\/jats:sub> receptor subtype (CHO\u2010M<jats:sub>3<\/jats:sub>). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC<jats:sub>50<\/jats:sub> of 14 \u03bc<jats:sc>M<\/jats:sc>. The muscarinic receptor antagonists 4\u2010DAMP, AF\u2010DX 384, pirenzepine and methroctamine inhibited the ACh\u2010induced calcium signal with the following respective IC<jats:sub>50<\/jats:sub> (pK<jats:sub>b<\/jats:sub>) values: 0.78 n<jats:sc>M<\/jats:sc> (9.1), 69 n<jats:sc>M<\/jats:sc> (7.2), 128 n<jats:sc>M<\/jats:sc> (7.1), and 2510 n<jats:sc>M<\/jats:sc> (5.8).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M<jats:sub>3<\/jats:sub> receptor subtype expression at the crypt\u2010base.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Otilonium bromide inhibited the generation of ACh\u2010induced calcium signals in a dose dependent manner (IC<jats:sub>50<\/jats:sub>=880 n<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In CHO\u2010M<jats:sub>3<\/jats:sub> cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine\u2010induced colonic crypt calcium signals.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present studies have demonstrated that OB inhibited M<jats:sub>3<\/jats:sub> receptor\u2010coupled calcium signals in human colonic crypts and CHO\u2010M<jats:sub>3<\/jats:sub> cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M<jats:sub>3<\/jats:sub> receptor\u2010coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti\u2010secretory action in IBS patients suffering with diarrhoea.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>137<\/jats:bold>, 1134\u20131142. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704942\">10.1038\/sj.bjp.0704942<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704942","type":"journal-article","created":{"date-parts":[[2002,11,12]],"date-time":"2002-11-12T18:47:25Z","timestamp":1037126845000},"page":"1134-1142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The colon\u2010selective spasmolytic otilonium bromide inhibits muscarinic M<sub>3<\/sub> receptor\u2010coupled calcium signals in isolated human colonic crypts"],"prefix":"10.1111","volume":"137","author":[{"given":"Susanne","family":"Lindqvist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hernon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Johns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Addison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Tighe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Greer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Mackay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Stebbings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Speakman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Evangelista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1998.00397.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.535"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/361315a0"},{"key":"e_1_2_7_5_1","first-page":"469","article-title":"Antagonist binding properties of five cloned muscarinic receptors expressed in CHO\u2010K1 cells","volume":"35","author":"BUCKLEY N.J.","year":"1989","journal-title":"Mol. 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