Multispecific amphipathic substrate transport by an organic anion transporter of human liver

J Hepatol. 1996 Nov;25(5):733-8. doi: 10.1016/s0168-8278(96)80246-7.


Background: Hepatic uptake of differently charged amphipathic endo- and xenobiotics is thought to occur via distinct carrier-mediated transport systems. Alternatively, a single rat organic anion transporting polypeptide (oatp) has recently been demonstrated to mediate hepatocellular uptake of differently charged amphipathic substrates.

Aim: To investigate whether a cloned human liver organic anion transporting polypeptide (OATP) also can mediate charge- and class-independent hepatocellular uptake of amphipathic substrates.

Methods: Xenopus laevis oocytes were injected with OATP-cRNA. Sodium-independent uptake of estrone-3-sulfate, ouabain and the organic cation N-(4,4-azo-n-pentyl)-21-ajmalinium was compared in OATP-expressing and uninjected (or water injected) control oocytes.

Results: Our results indicate that OATP, in addition to bromosulfophthalein and bile salts, can also transport anionic estrone-3-sulfate (Km approximately 59 microM), neutral ouabain (K(m) approximately 5.5 mM) and cationic N-(4,4-azo-n-pentyl)-21-ajmalinium. For each of these compounds, OATP-mediated uptake was cis-inhibited by the OATP substrate taurochenodeoxycholate and the transport activities correlated well with the amounts of cRNA injected.

Conclusion: Similar to the rat liver oatp, the human liver OATP can also mediate multispecific and charge-independent uptake of lipophilic amphipathic organic compounds. Thus, OATP may play an important role in the first pass clearance of drugs and other xenobiotics by the human liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anion Transport Proteins
  • Azo Compounds / metabolism
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • Electrochemistry
  • Female
  • Humans
  • Liver / metabolism*
  • Metabolic Clearance Rate
  • Oocytes / metabolism
  • Rats
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Substrate Specificity
  • Taurochenodeoxycholic Acid / metabolism
  • Xenobiotics / chemistry
  • Xenobiotics / metabolism*
  • Xenopus laevis


  • Anion Transport Proteins
  • Azo Compounds
  • Carrier Proteins
  • Xenobiotics
  • Taurochenodeoxycholic Acid