Functional analysis of rat renal organic anion transporter OAT-K1: bidirectional methotrexate transport in apical membrane.
Renal organic anion transporter OAT-K1 was stably transfected in MDCK cells and examined for its transport characteristics and membrane localization. OAT-K1 mediated both uptake and efflux of methotrexate in the apical membranes. Immunoblotting showed that the apparent molecular mass of the expressed OAT-K1 was 50 kDa, which was comparable to that found in the rat renal brush-border membranes. The OAT-K1-mediated methotrexate transport was significantly inhibited in the presence of several organic anions such as folate and sulfobromophthalein. These findings suggest that OAT-K1 mediates bidirectional methotrexate transport across the apical membranes, and may be involved in the renal handling of methotrexate.
Masuda
S
S
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Takeuchi
A
A
Saito
H
H
Hashimoto
Y
Y
Inui
K
K
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004285:Dogs; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008727:Methotrexate / Q000493:pharmacokinetics*; D008871:Microvilli / Q000378:metabolism; D009865:Oocytes; D027361:Organic Anion Transporters; D051381:Rats; D014162:Transfection; D014981:Xenopus
D002352:Carrier Proteins; D008565:Membrane Proteins; D027361:Organic Anion Transporters; C101140:Slc21a4 protein, rat; D008727:Methotrexate