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The aim of this study was to characterize expression, function, and cellular location of ACh\u2010related proteins in biopsies obtained from endoscopic normal\u2010appearing sigmoid colon in patients with and without CRN. Messenger\u2010RNA (mRNA) levels of 17 ACh\u2010related proteins were quantified by rt\u2010qPCR. Functional responses to ACh, measured as electrogenic transepithelial short circuit current (SCC), were recorded using the Ussing chamber technique. Finally, cellular localization of choline transporter\u2010like proteins (CTLs) and butyryl\u2010cholinesterase enzyme (BChE) was determined by immunohistochemistry. mRNA expression of <jats:italic>CTL1<\/jats:italic> and <jats:italic>CTL4<\/jats:italic> was increased in patients with CRN (<jats:italic>P<\/jats:italic>\u2009=\u20090.002 and <jats:italic>P<\/jats:italic>\u2009=\u20090.04, respectively). In functional experiments, baseline SCC was increased in CRN patients. ACh induced rapid biphasic changes in SCC. An initial decreasing phase was observed in the minority of CRN patients versus the majority of controls (25% vs 69%, respectively, <jats:italic>P<\/jats:italic>\u2009=\u20090.031). For the second increasing phase of SCC, data indicated ACh\u2010activation of two receptors. For both parts of the biphasic response, the half maximal effective concentration and maximal responses showed no difference between patient groups. Immunohistochemistry demonstrated CTL1, 3 and 4 and BChE to be localized to colonic crypt cells. We conclude that CRN is associated with increased expression of <jats:italic>CTL1<\/jats:italic> and <jats:italic>CTL4<\/jats:italic>, augmented basal prostaglandin\u2010dependent secretion, and altered functional channel response to ACh in human endoscopic normal\u2010appearing colonic mucosa. The immunohistochemical findings support CTL1, CTL3, CTL4, and BChE to be involved in non\u2010neuronal mucosal ACh metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22675","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T20:59:14Z","timestamp":1495573154000},"page":"2223-2233","source":"Crossref","is-referenced-by-count":11,"title":["Acetylcholine\u2010related proteins in non\u2010neoplastic appearing colonic mucosa from patients with colorectal neoplasia"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1282-3349","authenticated-orcid":false,"given":"Morten Matthiesen Bach","family":"Damm","sequence":"first","affiliation":[{"name":"Digestive Disease Center K Bispebjerg Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorbj\u00f8rn S\u00f8ren R\u00f8nn","family":"Jensen","sequence":"additional","affiliation":[{"name":"Digestive Disease Center K Bispebjerg Hospital 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