title: Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a membrane potential-driven organic anion transporter.
abstract: Membrane potential (Δψ)-driven and Cl(-)-dependent organic anion transport is a primary function of the solute carrier family 17 (SLC17) transporter family. Although the transport substrates and physiological relevance of the major members are well understood, SLC17A2 protein known to be Na(+)-phosphate cotransporter 3 (NPT3) is far less well characterized. In the present study, we investigated the transport properties and expression patterns of mouse SLC17A2 protein (mNPT3). Proteoliposomes containing the purified mNPT3 protein took up radiolabeled p-aminohippuric acid (PAH) in a Δψ- and Cl(-)-dependent manner. The mNPT3-mediated PAH uptake was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDs) and Evans blue, common inhibitors of SLC17 family members. The PAH uptake was also inhibited by various anionic compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs (NSAIDs) and urate. Consistent with these observations, the proteoliposome took up radiolabeled urate in a Δψ- and Cl(-)-dependent manner. Immunohistochemistry with specific antibodies against mNPT3 combined with RT-PCR revealed that mNPT3 is present in various tissues, including the hepatic bile duct, luminal membranes of the renal urinary tubules, maternal side of syncytiotrophoblast in the placenta, apical membrane of follicle cells in the thyroid, bronchiole epithelial cells in the lungs, and astrocytes around blood vessels in the cerebrum. These results suggested that mNPT3 is a polyspecific organic anion transporter that is involved in circulation of urate throughout the body.
authors.affiliation: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;
authors.forename: Natsuko
authors.initials: N
authors.lastname: Togawa
authors.affiliation: Advanced Science Research Center, Okayama University, Okayama, Japan; and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Narinobu
authors.initials: N
authors.lastname: Juge
authors.affiliation: Advanced Science Research Center, Okayama University, Okayama, Japan; and.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Miyaji
authors.affiliation: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;
authors.forename: Miki
authors.initials: M
authors.lastname: Hiasa
authors.affiliation: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Omote
authors.affiliation: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Advanced Science Research Center, Okayama University, Okayama, Japan; and moriyama@pharm.okayama-u.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Moriyama
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005786:Gene Expression Regulation; D006626:Hippurates / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D008810:Mice, Inbred C57BL; D050609:Sodium-Phosphate Cotransporter Proteins, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D002712:Chlorides; D006626:Hippurates; C493549:Slc17a2 protein, mouse; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D014527:Uric Acid; C030514:hippuric acid
keywords: Na+-phosphate cotransporter 3; organic anion transporter; polyspecific; solute carrier family 17 subtype A2; urate