Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6.
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Cui Y, Konig J, Leier I, Buchholz U, Keppler D
Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6.
J Biol Chem. 2001 Mar 30;276(13):9626-30. Epub 2000 Dec 27.
- PubMed ID
- 11134001 [ View in PubMed]
- Abstract
Bilirubin, the end product of heme catabolism, is taken up from the blood circulation into the liver. This work identifies a high-affinity transport protein mediating the uptake of bilirubin and its conjugates into human hepatocytes. Human embryonic kidney cells (HEK293) permanently expressing the recombinant organic anion-transporting polypeptide 2 (human OATP2, also known as LST-1 or OATP-C; symbol SLC21A6) showed uptake of [(3)H]monoglucuronosyl bilirubin, [(3)H]bisglucuronosyl bilirubin, and [(3)H]sulfobromophthalein with K(m) values of 0.10, 0.28, and 0.14 microm, respectively. High-affinity uptake of unconjugated [(3)H]bilirubin by OATP2 occurred in the presence of albumin and was not mediated by another basolateral hepatic uptake transporter, human OATP8 (symbol SLC21A8). OATP2 and OATP8 differed by their capacity to extract substrates from albumin before transport. In comparison to the high-affinity transport by OATP2, OATP8 transported [(3)H]sulfobromophthalein and [(3)H]monoglucuronosyl bilirubin with lower affinity, with K(m) values of 3.3 and 0.5 microm, respectively. The organic anion indocyanine green potently inhibited transport mediated by OATP2, with a K(i) value of 112 nm, but did not inhibit transport mediated by OATP8. Human OATP2 may play a key role in the prevention of hyperbilirubinemia by facilitating the selective entry of unconjugated bilirubin and its glucuronate conjugates into human hepatocytes.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cholic Acid Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorInducerDetails Cholic Acid Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateDetails Conjugated estrogens Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorDetails Conjugated estrogens Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateDetails Rifampicin Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownInhibitorDetails Rifampicin Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateInhibitorDetails Taurocholic acid Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorInducerDetails Taurocholic acid Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateDetails