Expression, transport properties, and chromosomal location of organic anion transporter subtype 3

The rat and mouse organic anion-transporting polypeptides (oatp) subtype 3 (oatp3) were cloned to further define components of the intestinal bile aci d transport system. In transfected COS cells, oatp3 mediated Na+-independen t, DIDS-inhibited taurocholate uptake (Michaelis-Menten constant similar to 30 muM). The oatp3-mediated uptake rates and affinities were highest for g lycine-conjugated dihydroxy bile acids. In stably transfected, polarized Ma din-Darby canine kidney (MDCK) cells, oatp3 mediated only apical uptake of taurocholate. RT-PCR analysis revealed that rat oatp3, but not oatp1 or oat p2, was expressed in small intestine. By RNase protection assay, oatp3 mRNA was readily detected down the length of the small intestine as well as in brain, lung, and retina. An antibody directed to the carboxy terminus local ized oatp3 to the apical brush-border membrane of rat jejunal enterocytes. The mouse oatp3 gene was localized to a region of mouse chromosome 6. This region is syntenic with human chromosome 12p12, where the human OATP-A gene was mapped, suggesting that rodent oatp3 is orthologous to the human OATP- A. These transport and expression properties suggest that rat oatp3 mediate s the anion exchange-driven absorption of bile acids previously described f or the proximal small intestine.