EFFECT OF NICOTINE ON RECTAL MUCUS AND MUCOSAL EICOSANOIDS

Because ulcerative colitis is largely a disease of non-smokers and nic otine may have a beneficial effect on the disease, the effect of nicot ine on rectal mucosa in rabbits was examined. Nicotine was given subcu taneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1. 1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 mu m) was significantly reduced by low dose (22 mu m, p=0.0011), and inc reased by high dose nicotine (48 mu m, p=0.035). Incorporation of radi oactive glucosamine into papain resistant glycoconjugates was unchange d, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF(1 alpha), PGF(2 alpha), and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence - with greatest inhibition in relation to t he lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secreti on in the rectum and large bowel.