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

• Published in: QJM : An International Journal of Medicine 2003-01, Vol.96 (1), p.57-65
• Main Authors: Richardson, C.E., Morgan, J.M., Jasani, B., Green, J.T., Rhodes, J., Williams, G.T., Lindstrom, J., Wonnacott, S., Peel, S., Thomas, G.A.O.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biopsy; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Colitis, Ulcerative - metabolism; Colon - drug effects; Colon - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Humans; In Situ Hybridization; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Male; Medical sciences; Middle Aged; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Prospective Studies; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - metabolism; Rectum - drug effects; Rectum - metabolism; Smoking - metabolism
• ISSN: 1460-2725; 1460-2393; 1460-2393
• DOI: 10.1093/qjmed/hcg007

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 α3 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 α3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of α3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium α3 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 α3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of α3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.