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Ulcerative colitis patients in remission have an altered secretory capacity in the proximal colon despite macroscopically normal mucosa

Journal article
Authors Jenny K Gustafsson
Gunnar C. Hansson
Henrik Sjövall
Published in Neurogastroenterology and Motility
Volume 24
Issue 8
Pages e381-e391
ISSN 1350-1925
Publication year 2012
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Medicine, Department of Internal Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages e381-e391
Language en
Links dx.doi.org/10.1111/j.1365-2982.2012...
Keywords carbachol, forskolin, mucus, ussing chamber, epithelial-cell line, cystic-fibrosis, chloride secretion, membrane, capacitance, cl-secretion, mouse model, transport, mechanism, conductance, exocytosis, ulsen jh, 1994, proceedings of the national academy of sciences of the united states of
Subject categories Basic Medicine

Abstract

Background One of the hallmarks of acute colitis is loss of epithelial transport. For unknown reasons, many patients still suffer from GI symptoms during remission, indicating a sustained imbalance between absorption and secretion. We hypothesize that the colonic epithelium becomes more reactive to secretagogues to compensate for a failing barrier. Methods Biopsies from ascending colon and sigmoid colon of UC patients in remission and controls were mounted in Ussing chambers. Membrane current (Im) and epithelial capacitance (Cp) were used as markers for anion secretion and mucus exocytosis. Carbachol (1 mmol L-1) and forskolin (10 mu mol L-1) were used to study Ca2+ and cAMP-mediated secretion. Key Results Baseline values showed segmental patterns with higher Im in ascending colon and higher Cp in sigmoid colon of both UC patients and controls, but the patterns did not differ between the groups. The Im response to forskolin was increased (+35%) in the ascending colon of UC patients and the Im response to carbachol was decreased (-40%) in the same segment. No group differences were seen in the distal colon for either the forskolin or carbachol-induced Im responses. The Cp response to carbachol was instead up-regulated in the distal colon of UC patients, but remained unaffected in the proximal colon. Conclusions & Inferences The proximal colonic mucosa of UC patients in remission seems to shift its reactivity to secretagogues, becoming more sensitive to cAMP-dependent secretion and less sensitive to Ca2+-dependent secretion. This phenomenon may contribute to residual diarrhea in this patient group, despite resolution of inflammation.

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