Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver.
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Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B
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.
- PubMed ID
- 11159893 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Liothyronine Thyroid hormone receptor beta Protein Humans YesAgonistDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Estradiol acetate Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Estradiol acetate UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Estradiol benzoate Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Estradiol benzoate UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Estradiol cypionate Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Estradiol cypionate UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Estradiol dienanthate Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Estradiol dienanthate UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Estradiol valerate Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Estradiol valerate UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Quinine Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails - Drug Transporters