p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1.
Organic anions are secreted into urine via organic anion transporters across the renal basolateral and apical membranes. However, no apical membrane transporter for organic anions such as p-aminohippuric acid (PAH) has yet been identified. In the present study, we showed that human NPT1, which is present in renal apical membrane, mediates the transport of PAH. The K(m) value for PAH uptake was 2.66 mM and the uptake was chloride ion sensitive. These results are compatible with those reported for the classical organic anion transport system at the renal apical membrane. PAH transport was inhibited by various anionic compounds. Human NPT1 also accepted uric acid, benzylpenicillin, faropenem, and estradiol-17beta-glucuronide as substrates. Considering its chloride ion sensitivity, Npt1 is expected to function for secretion of PAH from renal proximal tubular cells. This is the first molecular demonstration of an organic anion transport function for PAH at the renal apical membrane.
Uchino
H
H
Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan.
Tamai
I
I
Yamashita
K
K
Minemoto
Y
Y
Sai
Y
Y
Yabuuchi
H
H
Miyamoto
K i
Ki
Takeda
E
E
Tsuji
A
A
D000838:Anions / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000838:Anions; D002352:Carrier Proteins; D010710:Phosphates; D011994:Recombinant Proteins; C493546:SLC17A1 protein, human; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D010130:p-Aminohippuric Acid