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Q J Med 2003; 96: 57-65
© 2003 Association of Physicians

Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis

C.E. Richardson1, J.M. Morgan2, B. Jasani2, J.T. Green1, J. Rhodes1,, G.T. Williams2, J. Lindstrom3, S. Wonnacott4, S. Peel5 and G.A.O. Thomas1

From the Departments of 1 Gastroenterology and 2 Pathology, University Hospital of Wales, Cardiff, UK, 3 Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, USA, 4 Department of Biology and Biochemistry, University of Bath, Bath, and 5 Department of Human Morphology, Medical School, University of Southampton, Southampton, UK

Received 4 January 2002 and in revised form 4 November 2002

Background: Ulcerative colitis (UC) is a disease largely of non-smokers, in which nicotine is of therapeutic value. The mode of action is unknown, but may involve nicotinic acetylcholine receptors (nAChRs) in the bowel wall.

Aim: To investigate the presence of nAChRs in rectal mucosa, and the effect of smoking and nicotine on their expression.

Design: Prospective case-control study.

Methods: In situ hybridization (ISH) and immunocytochemistry (ICC) were used to show {alpha}3 nAChRs in colonic mucosa. Rectal mucosa was examined from controls (n=55) and patients with inactive UC (n=62), both smokers and non-smokers, by ICC, using two antibodies to show the density and distribution of receptors in the mucosa. Non-smokers with UC (n=43) were given transdermal nicotine or placebo patches for 6 months, and rectal biopsies, taken before and after treatment, were examined by ICC to show nAChRs.

Results: In normal colon, ISH and ICC showed {alpha}3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of {alpha}3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium {alpha}3 subunit, compared with UC patients.

Discussion: The presence of nAChRs in colonic epithelium may be pertinent to the beneficial effect of nicotine in UC, but since neither smoking nor nicotine treatment is associated with any change in the expression of epithelial {alpha}3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of {alpha}3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.

Address correspondence to Professor John Rhodes, Department of Gastroenterology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW


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