Organic Anion-Transporting Polypeptide B (OATP-B) and Its Functional Comparison With Three Other OATPs of Human Liver

Gastroenterology. 2001 Feb;120(2):525-33. doi: 10.1053/gast.2001.21176.

Abstract

Background & aims: Hepatic uptake of cholephilic organic compounds is mediated by members of the organic anion-transporting polypeptide (OATP) family. We aimed to characterize the novel OATP-B with respect to tissue distribution and hepatocellular localization and to compare its substrate specificity with those of OATP-A, OATP-C, and OATP8.

Methods: Tissue distribution and hepatocellular localization of OATP-B were analyzed by Northern blotting and immunofluorescence, respectively. Transport of 16 substrates was measured for each individual human OATP in complementary RNA-injected Xenopus laevis oocytes.

Results: Expression of OATP-B was most abundant in human liver, where it is localized at the basolateral membrane of hepatocytes. OATP-B, OATP-C, and OATP8 mediated high-affinity uptake of bromosulphophthalein (K(m), approximately 0.7, 0.3, and 0.4 micromol/L, respectively). OATP-B also transported estrone-3-sulfate but not bile salts. Although OATP-A, OATP-C, and OATP8 exhibit broad overlapping substrate specificities, OATP8 was unique in transporting digoxin and exhibited especially high transport activities for the anionic cyclic peptides [D-penicillamine(2,5)]enkephalin (DPDPE; opioid-receptor agonist) and BQ-123 (endothelin-receptor antagonist).

Conclusions: OATP-B is the third bromosulphophthalein uptake system localized at the basolateral membrane of human hepatocytes. OATP-B, OATP-C, and OATP8 account for the major part of sodium-independent bile salt, organic anion, and drug clearance of human liver.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anion Transport Proteins
  • Anions / pharmacokinetics
  • Antibodies
  • Arylsulfatases / pharmacokinetics
  • Biological Transport / physiology
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Coloring Agents / pharmacokinetics
  • DNA, Complementary
  • Estrone / analogs & derivatives*
  • Estrone / pharmacokinetics
  • Gene Expression / physiology
  • Humans
  • Liver / chemistry
  • Liver / metabolism*
  • Molecular Weight
  • Oocytes / physiology
  • RNA, Messenger / analysis
  • Rabbits
  • Steryl-Sulfatase
  • Sulfobromophthalein / pharmacokinetics
  • Xenopus laevis

Substances

  • Anion Transport Proteins
  • Anions
  • Antibodies
  • Carrier Proteins
  • Coloring Agents
  • DNA, Complementary
  • RNA, Messenger
  • Sulfobromophthalein
  • Estrone
  • Arylsulfatases
  • Steryl-Sulfatase
  • estrone sulfate