DIFFERENTIAL EFFECT OF URSODEOXYCHOLATE AND ITS TAURINE CONJUGATE ON BILIARY TRANSPORT MAXIMUM OF BILIRUBIN IN THE RAT

The effects of ursodeoxycholate and its taurine conjugate on biliary T m of bilirubin were evaluated in rats. Ursodeoxycholate was administer ed at four different doses (4, 8, 12 or 16 mu mol per 100 g body wt i. v., followed by an i.v. infusion of 0.3, 0.6, 0.9 or 1.2 mu mol/min pe r 100 g body wt, respectively), whereas tauroursodeoxycholate was admi nistered only at the maximal dose. A dose-dependent diminution of bili rubin Tm was observed during ursodeoxycholate administration, which ra nged from no effect at the lowest dose to a virtual excretory blockage at the highest dose. This was associated with an increase in bilirubi n concentrations in both plasma and liver as well as in the fractional amount of conjugated pigment in both sites, suggesting an impairment of bilirubin transfer at the canalicular level. Incomplete taurine con jugation of ursodeoxycholate well correlated with these effects. Unlik e ursodeoxycholate, tauroursodeoxycholate had no inhibitory effect on bilirubin Tm, although a slight inhibition of bilirubin uptake and bil irubin conjugation became apparent. Taken together, these results sugg est that ursodeoxycholate interferes with the hepatobiliary transport of bilirubin by impairing its transfer at the canalicular level and th at incomplete taurine conjugation appears to be a key factor determini ng this effect.