Transport of the sulfated, amidated bile acid, sulfolithocholyltaurine, into rat hepatocytes is mediated by Oatp1 and Oatp2

Hepatology. 2002 May;35(5):1031-40. doi: 10.1053/jhep.2002.32667.


The uptake of the sulfated bile acid sulfolithocholyltaurine (SLCT) was investigated in isolated rat hepatocytes and in HeLa cells transfected with complementary DNAs (cDNAs) of organic anion transporting polypeptides (Oatps) 1 and 2 cloned from rat liver. In hepatocytes, transport of SLCT was greatly reduced by bromosulfophthalein (BSP), estrone sulfate, the precursor bile acids cholyltaurine and lithocholyltaurine, and 4,4'-diisothiocyanostilbene-2-2'-disulfonic acid (DIDS). However, SLCT transport was insensitive to 4-methylumbelliferyl sulfate, harmol sulfate, digoxin, fexofenadine, and lack of sodium ion. Because the estimation of kinetic constants was enhanced with use of inhibitors, BSP (1-50 micromol/L) was added to isolated rat hepatocytes to assess the various transport components for SLCT uptake. The resulting data showed a nonsaturable pathway and at least 2 pathways of different Michaelis-Menten constants (K(m)) (70 and 6 micromol/L) and similar maximum velocities (V(max)) (1.73 and 1.2 nmol/min/mg protein) and inhibition constants of 0.63 and 10.3 micromol/L for BSP. In expression systems, SLCT was taken up by Oatp1 and Oatp2 expressed in HeLa cells with similar K(m) values (12.6 +/- 6.2 and 14.6 +/- 1.9 micromol/L). These K(m) values were comparable to that observed for the high-affinity pathway in rat hepatocytes. In conclusion, the results suggest that transport of SLCT into rat liver is mediated in part by Oatp1 and Oatp2, high-affinity pathways, a lower-affinity pathway of unknown origin, and a nonsaturable pathway that is compatible with a transport system of high K(m) and/or passive diffusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anions / pharmacology
  • Cholagogues and Choleretics / pharmacokinetics*
  • Choline / pharmacology
  • Gene Expression
  • HeLa Cells
  • Hepatocytes / metabolism*
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents / pharmacology
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Liver-Specific Organic Anion Transporter 1 / metabolism
  • Male
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfates / pharmacokinetics*
  • Sulfobromophthalein / pharmacology
  • Taurolithocholic Acid / pharmacokinetics*
  • Temperature


  • Anions
  • Cholagogues and Choleretics
  • Indicators and Reagents
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters, Sodium-Independent
  • Slco1a1 protein, rat
  • Sulfates
  • Sulfobromophthalein
  • Taurolithocholic Acid
  • Choline