Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6.

Article Details

Citation

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
DrugTransporterKindOrganismPharmacological ActionActions
Cholic AcidSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Cholic AcidSolute carrier organic anion transporter family member 1B3ProteinHumans
Unknown
Substrate
Details
Conjugated estrogensSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Details
Conjugated estrogensSolute carrier organic anion transporter family member 1B3ProteinHumans
Unknown
Substrate
Details
RifampicinSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Inhibitor
Details
RifampicinSolute carrier organic anion transporter family member 1B3ProteinHumans
Unknown
Substrate
Inhibitor
Details
Taurocholic acidSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Taurocholic acidSolute carrier organic anion transporter family member 1B3ProteinHumans
Unknown
Substrate
Details