Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells.
Article Details
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Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G
Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells.
J Biol Chem. 1999 Jan 15;274(3):1519-24.
- PubMed ID
- 9880528 [ View in PubMed]
- Abstract
Organic anion transporters play an essential role in eliminating a wide range of organic anions including endogenous compounds, xenobiotics, and their metabolites from kidney, thereby preventing their potentially toxic effects within the body. The goal of this study was to extend our previous study on the functional characterization and post-translational modification of a mouse kidney organic anion transporter (mOAT), in a mammalian cell system, COS-7 cells. The transporter-mediated p-aminohippurate (PAH) uptake was saturable, probenecid-sensitive, and inhibited by a wide range of organic anions including vitamins, anti-hypertensive drugs, anti-tumor drugs, and anti-inflammatory drugs. Tunicamycin, an inhibitor of asparagine-linked glycosylation, significantly inhibited the transport activity. Immunofluorescence provided evidence that most of the protein remained in the intracellular compartment in tunicamycin-treated cells. Diethyl pyrocarbonate (DEPC), a histidine residue-specific reagent, completely blocked PAH transport. The inhibitory effect by DEPC was significantly protected (90%) by pretreating the cells with excess unlabeled PAH, suggesting that the histidine residues may be close to the PAH binding sites. Finally, in situ mRNA localization was studied in postnatal mouse kidney. The expression was observed in proximal tubules throughout development. We conclude that COS-7 cells may be useful in pharmacological and molecular biological studies of this carrier. The carbohydrate moieties are necessary for the proper trafficking of mOAT to the plasma membrane, and histidine residues appear to be important for the transport function.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Aminohippuric acid Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Captopril Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Carprofen Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Diclofenac Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Enalapril Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Folic acid Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Indomethacin Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Methotrexate Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Probenecid Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Riboflavin Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Sulindac Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails