Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta

A cDNA encoding a novel multispecific organic anion transporter, OAT4, was isolated from a human kidney cDNA library, The OAT4 cDNA consisted of 2210 base pairs that encoded a 550-amino acid residue protein with 12 putative m embrane-spanning domains. The amino acid sequence of OAT4 showed 38 to 44% identity to those of other members of the OAT family. Northern blot analysi s revealed that OAT4 mRNA is abundantly expressed in the placenta as well a s in the kidney. When expressed in Xenopus oocytes, OAT4 mediated the high affinity transport of estrone sulfate (K-m = 1.01 mu M) and dehydroepiandro sterone sulfate (K-m = 0.63 mu M) in a sodium-independent manner. OAT4 also mediated the transport of ochratoxin A. OAT4-mediated transport of estrone Sulfate was inhibited by several sulfate conjugates, such as p-nitrophenyl sulfate, alpha-naphthyl sulfate, beta-estradiol sulfate, and 4-methylumbel liferyl sulfate. By contrast, glucuronide conjugates showed little or no in hibitory effect on the OAT4-mediated transport of estrone sulfate. OAT4 int eracted with chemically heterogeneous anionic compounds, such as nonsteroid al antiinflammatory drugs, diuretics, sulfobromophthalein, penicillin G, an d bile salts, whereas tetraethylammonium, an organic cation, did not. OAT4 is the first member of the multispecific organic anion transporter family, which is expressed abundantly in the placenta. OAT4 might be responsible fo r the elimination and detoxification of harmful anionic substances from the fetus.