Organic anion-transporting potypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver

Background & Aims: Hepatic uptake of cholephilic organic compounds is media ted by members of the organic anion-transporting polypeptide (OATP) family. We aimed to characterize the novel OATP-B with respect to tissue distribut ion and hepatocellular localization and to compare its substrate specificit y with those of OATP-A, OATP-C, and OATP8. Methods: Tissue distribution and hepatocellular localization of OATP-B were analyzed by Northern blotting a nd immunofluorescence, respectively. Transport of 16 substrates was measure d for each individual human OATP in complementary RNA-injected Xenopus laev is 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, similar to0.7, 0.3, and 0.4 mu mol/L, respectively). OATP-B also transpo rted estrone-3-sulfate but not bile salts. Although OATP-A, OATP-C, and OAT P8 exhibit broad overlapping substrate specificities, OATP8 was unique in t ransporting 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 b asolateral membrane of human hepatocytes. OATP-B, OATP-C, and OATP8 account for the major part of sodium-independent bile salt, organic anion, and dru g clearance of human liver.