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


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


METHODS
Prospective case-control study.


METHODS
In situ hybridization (ISH) and immunocytochemistry (ICC) were used to show alpha3 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 alpha3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of alpha3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium alpha3 subunit, compared with UC patients.


CONCLUSIONS
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 alpha3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of alpha3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.
Richardson
C E
CE
Department of Gastroenterology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, Wales, UK.
Morgan
J M
JM
Jasani
B
B
Green
J T
JT
Rhodes
J
J
Williams
G T
GT
Lindstrom
J
J
Wonnacott
S
S
Peel
S
S
Thomas
G A O
GA
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011446:Prospective Studies; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D012007:Rectum / Q000187:drug effects / Q000378:metabolism; D012907:Smoking / Q000378:metabolism*
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine