J. Konig et al., Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide, J BIOL CHEM, 275(30), 2000, pp. 23161-23168
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.