A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane

We cloned and expressed a new organic anion transporting polypeptide (OATP) , termed human OATP2, (OATP-C, LST-1; symbol SLC21A6), involved in the upta ke of various lipophilic anions into human liver. The cDNA encoding OATP2 c omprised 2073 base pairs, corresponding to a protein of 691 amino acids, wh ich were 44% identical to the known human OATP. An antibody directed agains t the carboxy terminus localized OATP2 to the basolateral membrane of human hepatocytes. Northern blot analysis indicated a strong expression of OATP2 only in human liver. Transport mediated by recombinant OATP2 and its local ization were studied in stably transfected Madin-Darby canine kidney strain II (MDCKII) and HEK293 cells. Confocal microscopy localized recombinant OA TP2 protein to the lateral membrane of MDCKII cells. Substrates included 17 beta-glucuronosyl estradiol, monoglucuronosyl bilirubin, dehydroepiandrost erone sulfate, and cholyltaurine. 17 beta-Glucuronosyl estradiol was a pref erred substrate, with a Michaelis-Menten constant value of 8.2 mu M; its up take was Na+ independent and was inhibited by sulfobromophthalein, with a i nhibition constant value of 44 nM. Our results indicate that OATP2 is impor tant for the uptake of organic anions, including bilirubin conjugates and s ulfobromophthalein, in human liver.