EFFECT OF NICOTINE ON GALLBLADDER BILE

Several studies have shown that symptomatic gallstones are largely a d isease of nonsmokers, which raises the possibility that nicotine may p rotect against the formation of gallstones. To examine the effect of n icotine on the gallbladder, 32 rabbits were allocated to four groups: controls and three treatment groups in which nicotine tartarate at low , medium and high doses was administered subcutaneously via an osmotic minipump. After 14 days' treatment the gallbladder was removed and me asurements made of gallbladder mucin synthesis, bile mucin concentrati on, bile acid concentration and cholesterol saturation. Serum nicotine concentrations (ng/mL) were (+/- SE) 0.4+/-0.1, 3.5+/-0.4, 8.8+/-0.8 and 16.2+/-1.8 in the controls and three treatment groups, respectivel y. Total bile acid concentration increased significantly in all three treated groups with the greatest increase in the group given low dose nicotine (P<0.001). Cholesterol saturation did not differ significantl y in any group but soluble mucin concentration in gallbladder bile was significantly reduced (P=0.013, 95% Cl: 16 to 111) with high dose nic otine. Gallbladder mucin synthesis, measured by H-3-glucosamine incorp oration, did not change significantly with nicotine treatment. Subcuta neous nicotine 2.0 mg/kg/day for 14 days significantly reduced the con centration of biliary mucin, which could potentially reduce cholestero l nucleation and subsequent gallstone formation. This may be one of th e mechanisms responsible for the relative reduction in gallstone disea se among smokers.