The effect of 3-sulphation and taurine conjugation on the uptake of chenodeoxycholic acid by rat hepatocytes.
The hepatic uptake of chenodeoxycholic acid, taurochenodeoxycholic acid, chenodeoxycholic acid 3-sulphate and taurochenodeoxycholate acid 3-sulphate by isolated rat hepatocytes was examined. Taurochenodeoxycholic acid, taurochenodeoxycholic acid 3-sulphate and chenodeoxycholic acid 3-sulphate uptake occurred by a saturable, energy-dependent process while chenodeoxycholic acid uptake was predominantly non-saturable, possibly simple diffusion. Apparent Km (mumol/l) and Vmax (nmol/mg protein per min) values (mean +/- S.D.), respectively, were: chenodeoxycholic acid (saturable component), 33 +/- 6.4 and 4.8 +/- 0.6; taurochenodeoxycholic acid, 11.1 +/- 2.0 and 3.1 +/- 0.5; chenodeoxycholic acid 3-sulphate, 6.1 +/- 0.9 and 2.3 +/- 0.4; and taurochenodeoxycholic acid 3-sulphate, 5.0 +/- 0.7 and 0.9 +/- 0.15. Both conjugation with taurine and sulphation at the 3 position resulted in a reduction in the values of Km and Vmax. Uptake of each of the bile acids taurochenodeoxycholic acid, taurochenodeoxycholic acid 3-sulphate and chenodeoxycholic acid 3-sulphate was competitively inhibited by the other two, with taurochenodeoxycholic acid a potent inhibitor of both taurochenodeoxycholic acid 3-sulphate and chenodeoxycholic acid 3-sulphate uptake. Other bile acids also inhibited. Uptake was inhibited by albumin in the order chenodeoxycholic acid 3-sulphate greater than taurochenodeoxycholic acid 3-sulphate greater than taurochenodeoxycholic acid and was dependent on the extent of bile acid binding to albumin.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*
D001647:Bile Acids and Salts; D013431:Sulfates; D002635:Chenodeoxycholic Acid; D013654:Taurine