Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver
| Autor: | Gerd A. Kullak-Ublick, Bruno Hagenbuch, Bruno Stieger, Lukas Landmann, Flavia Pizzagalli, Manfred G. Ismair, Peter J. Meier, Robert Huber, Karin Fattinger |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Anions
DNA Complementary Estrone Anion Transport Proteins Xenopus Gene Expression Antibodies Sulfobromophthalein Xenopus laevis medicine Animals Humans RNA Messenger Coloring Agents Arylsulfatases Epithelial polarity chemistry.chemical_classification Hepatology biology Chemistry Gastroenterology Biological Transport Blotting Northern biology.organism_classification Cyclic peptide Transport protein Molecular Weight Blot Organic anion-transporting polypeptide medicine.anatomical_structure Liver Biochemistry Hepatocyte Oocytes biology.protein Steryl-Sulfatase Rabbits Carrier Proteins Organic anion |
| Zdroj: | Gastroenterology. 120:525-533 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/gast.2001.21176 |
| Popis: | 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 (Km, ~0.7, 0.3, and 0.4 μmol/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-penicillamine2,5]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. GASTROENTEROLOGY 2001;120:525-533 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|