MEMBRANE TRANSPORT STRUCTURE FUNCTION AND BIOGENESIS
Hepatic Uptake of Bilirubin and Its Conjugates by the Human Organic Anion Transporter SLC21A6*

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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 [3H]monoglucuronosyl bilirubin, [3H]bisglucuronosyl bilirubin, and [3H]sulfobromophthalein withKm values of 0.10, 0.28, and 0.14 μm, respectively. High-affinity uptake of unconjugated [3H]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 [3H]sulfobromophthalein and [3H]monoglucuronosyl bilirubin with lower affinity, withKm values of 3.3 and 0.5 μm, respectively. The organic anion indocyanine green potently inhibited transport mediated by OATP2, with a Ki 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.

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Published, JBC Papers in Press, December 27, 2000, DOI 10.1074/jbc.M004968200

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The work was supported in part by Deutsche Forschungsgemeinschaft through SFB601 and the Fonds der Chemischen Industrie.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.