Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat.

Abstract

It has been reported that biliary secretion is the limiting step in the hepatic transport of bile acids by the hepatocyte from plasma to canalicular bile. The aim of the present study was to examine the role of conjugation in the transport process using ursodeoxycholate (UDCA) and tauroursodeoxycholate (TUDCA), two bile acid with low liver toxicity. Rats were given constant intravenous infusions of cholate (C), taurocholate (TC), UDCA, or TUDCA at progressively increasing rates. The biliary maximum secretory rate (SRm), in nmol . min-1 . 100 g body wt-1, for TC (1,835.2 +/- 135.5, mean +/- SE) was not significantly different from that of C (1,749.4 +/- 85.6). In contrast, the SRm for TUDCA (5,909.4 +/- 304.4) was approximately sevenfold that of UDCA (802.1 +/- 134.2), the difference being statistically significant (P less than 0.001). The SRm of UDCA in the presence of a taurine infusion (1,367 +/- 84.4) was higher than that of UDCA infused alone but still much lower than that of TUDCA. Phenobarbital sodium pretreatment did not increase SRm of UDCA alone or in the presence of a taurine infusion. These results suggest that in the rat 1) conjugation is the rate-limiting step in the overall transport of UDCA (and perhaps other bile acids) by the liver, and 2) the conjugation process itself is limiting, rather than the availability of taurine. They support the view that, although not mandatory for secretion into bile, conjugation of bile acids confers a biological advantage, possibly by increasing the solubility of the bile acid.