Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide

Based on sequence homology to the human organic anion transporting polypept ide 2 (OATPB; SLC21A6), we cloned a new member of the SLC21A superfamily of solute carriers, termed OATP8 (SLC21A8). The protein of 702 amino acids sh owed an amino acid identity of 80% with human OATPS, Based on Northern blot ting, the expression of OATP8 was restricted to human liver. Cosmid clones containing the genes encoding human OATP1 (SLC21A3), OATP2 (SLC21A6), and O ATP8 (SLC21AS) served to establish their genomic organization. All three ge nes contained 14 exons with 13 identical splice sites when transferred to t he amino acid sequence. An antibody raised against the carboxyl terminus lo calized OATP8 to the basolateral membrane of human hepatocytes and the reco mbinant glyeoprotein, expressed in MDCKII cells, to the lateral membrane, T ransport properties of OATP8 were studied in stably transfected MDCKII and HEH293 cells. Organic anions transported by human OATP8 included sulfobromo phthalein, with a K-m of 3.3 mu M, and17 beta-glucuronosyl estradiol, with a K-m of 5.4 mu M Several bile salts were not substrates. Thus, human OATPS is a new uptake transporter in the basolateral hepatocyte membrane with an overlapping but distinct substrate specificity as compared with OATP2, whi ch is localized to the same membrane domain.