Cloning and functional characterization of the pig (Sus scrofa) organic anion transporting polypeptide 1a2

1. Organic anion transporting polypeptides (OATPs) are a family of transporter proteins that have been extensively recognized as key determinants of absorption, distribution, metabolism and excretion of various drugs. Human OATP1A2 has been demonstrated to transport wide spectrum of endogenous and exogenous compounds. Study on OATP1A2 orthologues of other species, however, is still limited. 2. Here, we described the cloning and functional characterization of a member of the OATP/Oatp family member obtained from pig (Sus scrofa) liver. Sequence analysis suggested that it has a high homology with human OATP1A2 and bovine Oatp1a2. Prototypic substrates estrone-3-sulfate (E-3-S) and taurocholic acid were transported by the protein. The transport of these two substrates is pH-dependent, with lower pH showing higher uptake function. Kinetic study showed the transport of these two substrates have a Km of 42.5 ± 12.1 and 33.1 ± 8.7 µM, respectively. Pig Slco1a2 has the highest expression level in the liver, and to a less extend in the brain and small intestine. 3. In conclusion, an OATP member was cloned from pig liver. Sequence analysis and phylogenic study revealed it as an orthologue of human OATP1A2. Its kinetic characteristic for prototypic substrates and organ distribution are similar with that of OATP1A2.