Increased severity of experimental colitis in alphaS nicotinic acetylcholine receptor subunit-deficient mice

Substantial evidence suggests a negative association between cigarette smoking and the incidence and severity of ulcerative colitis, a common human inflammatory bowel disease. Nicotine has been implicated in this association. The detection of nicotinic acetylcholine receptors in colonic epithelium, the primary tissue affected in ulcerative colitis, suggests a role for these receptors in the beneficial effect of nicotine on colonic inflammation. Using an animal model, we demonstrate for the first time that alpha 5 nicotinic acetylcholine receptor knockout mice have significantly more severe experimental colitis than wild-type controls and that nicotine significantly ameliorates its course when compared with wild-type controls. These findings suggest that alpha 5-containing nicotinic acetylcholine receptors participate in the modulation of colitis in mice, but other nicotinic acetylcholine receptor subunits also mediate the antiinflammatory effects of nicotine.