title: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Zurich, Switzerland.
authors.forename: G A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: M G
authors.initials: MG
authors.lastname: Ismair
authors.forename: B
authors.initials: B
authors.lastname: Stieger
authors.forename: L
authors.initials: L
authors.lastname: Landmann
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: F
authors.initials: F
authors.lastname: Pizzagalli
authors.forename: K
authors.initials: K
authors.lastname: Fattinger
authors.forename: P J
authors.initials: PJ
authors.lastname: Meier
authors.forename: B
authors.initials: B
authors.lastname: Hagenbuch
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D000838:Anions / Q000493:pharmacokinetics; D000906:Antibodies; D001192:Arylsulfatases / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D004396:Coloring Agents / Q000493:pharmacokinetics; D018076:DNA, Complementary; D004970:Estrone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D009865:Oocytes / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D043266:Steryl-Sulfatase; D013448:Sulfobromophthalein / Q000493:pharmacokinetics; D014982:Xenopus laevis
chemical_list: D027321:Anion Transport Proteins; D000838:Anions; D000906:Antibodies; D002352:Carrier Proteins; D004396:Coloring Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; D013448:Sulfobromophthalein; D004970:Estrone; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; C017296:estrone sulfate