The choleretic effects of N-acetylglucosaminides, major urinary metabolites of ursodeoxycholic acid, in bile fistula rats

We investigated the effects of three bile acids conjugated with N-acetylglu cosamine, ursodeoxycholate N-acetylglucosaminide, tauroursodeoxycholate N-a cetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, on bile flow and biliary excretion of various markers in comparison with ursodeoxy cholic acid, tauroursodeoxycholic acid and glycoursodeoxycholic acid in bil e fistula rats. These bile acids were infused intravenously at a constant r ate of 0.3 or 0.6 mu mol/min/100 g b.w. for 2 h. All bile acids examined in creased bile flow in a dose-dependent manner. In particular, ursodeoxychola te N-acetylglucosaminide has a longer-lasting effect after its infusion on bile flow than the other bile acids. Furthermore, these bile acids markedly increased biliary total bile acid excretion. At a higher dose level, the c oefficient of determination (r(2)) between the biliary total bile acid excr etion and bile flow for ursodeoxycholate N-acetylglucosaminide (r(2) = 0.39 ) was lower than that for the other bile acids (r(2) = 0.75-0.92). The urso deoxycholate N-acetylglucosaminide, as well as tauroursodeoxycholic acid, g lycoursodeoxycholic acid, tauroursodeoxycholate N-acetylglucosaminide and g lycoursodeoxycholate N-acetylglucosaminide, was mostly excreted in an uncha nged form in bile, whereas ursodeoxycholic acid was excreted as a conjugate with taurine. The three N-acetylglucosaminides as well as ursodeoxycholic acid, tauroursodeoxycholic acid and glycoursodeoxycholic acid significantly increased the biliary excretion of cholesterol, phospholipid, bilirubin an d total Ca2+. In contrast, the N-acetylglucosaminides significantly decreas ed in biliary bicarbonate concentration, whereas ursodeoxycholic acid signi ficantly increased biliary bicarbonate concentration. However, tauroursodeo xycholic acid and glycoursodeoxycholic acid did not significantly change th e biliary bicarbonate concentration. The results indicate that N-acetylgluc osaminides have a choleretic effect in bile fistula rats. Our present study also demonstrates that N-acetylglucosaminides, but not ursodeoxycholic aci d, tauroursodeoxycholic acid or glycoursodeoxycholic acid, can significantl y reduce the biliary bicarbonate concentration. Furthermore, our findings s uggest that ursodeoxycholate N-acetylglucosaminide may partly exert a chole retic effect via mechanisms different from those of the other bile acids. ( C) 1998 Elsevier Science B.V. All rights reserved.