Functional analysis of rat renal organic anion transporter OAT-K1: Bidirectional methotrexate transport in apical membrane

Satohiro Masuda; Ayako Takeuchi; Hideyuki Saito; Yukiya Hashimoto; Ken Ichi Inui

doi:10.1016/S0014-5793(99)01221-1

Functional analysis of rat renal organic anion transporter OAT-K1: Bidirectional methotrexate transport in apical membrane

Satohiro Masuda, Ayako Takeuchi, Hideyuki Saito, Yukiya Hashimoto, Ken Ichi Inui^*

^*Corresponding author for this work

Clinical Pharmacokinetics

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

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. Copyright (C) 1999 Federation of European Biochemical Societies.

Original language	English
Pages (from-to)	128-132
Number of pages	5
Journal	FEBS Letters
Volume	459
Issue number	1
DOIs	https://doi.org/10.1016/S0014-5793(99)01221-1
State	Published - 1999/10/01

Keywords

Brush-border membrane
MDCK cell
Methotrexate
Organic anion transporter
Rat kidney
Tubular secretion

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(99)01221-1

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title = "Functional analysis of rat renal organic anion transporter OAT-K1: Bidirectional methotrexate transport in apical membrane",

abstract = "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. Copyright (C) 1999 Federation of European Biochemical Societies.",

keywords = "Brush-border membrane, MDCK cell, Methotrexate, Organic anion transporter, Rat kidney, Tubular secretion",

author = "Satohiro Masuda and Ayako Takeuchi and Hideyuki Saito and Yukiya Hashimoto and Inui, {Ken Ichi}",

note = "Funding Information: We thank Dr. P. Agre, Department of Biological Chemistry and Medicine, School of Medicine, Johns Hopkins University, for providing the plasmid XβG expression vector. This work was supported by a Grand-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, by a Grand-in-Aid from the Japan Research Foundation for Clinical Pharmacology, and from the Uehara Memorial Foundation.",

year = "1999",

month = oct,

day = "1",

doi = "10.1016/S0014-5793(99)01221-1",

language = "英語",

volume = "459",

pages = "128--132",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "1",

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TY - JOUR

T1 - Functional analysis of rat renal organic anion transporter OAT-K1

T2 - Bidirectional methotrexate transport in apical membrane

AU - Masuda, Satohiro

AU - Takeuchi, Ayako

AU - Saito, Hideyuki

AU - Hashimoto, Yukiya

AU - Inui, Ken Ichi

N1 - Funding Information: We thank Dr. P. Agre, Department of Biological Chemistry and Medicine, School of Medicine, Johns Hopkins University, for providing the plasmid XβG expression vector. This work was supported by a Grand-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, by a Grand-in-Aid from the Japan Research Foundation for Clinical Pharmacology, and from the Uehara Memorial Foundation.

PY - 1999/10/1

Y1 - 1999/10/1

N2 - 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. Copyright (C) 1999 Federation of European Biochemical Societies.

AB - 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. Copyright (C) 1999 Federation of European Biochemical Societies.

KW - Brush-border membrane

KW - MDCK cell

KW - Methotrexate

KW - Organic anion transporter

KW - Rat kidney

KW - Tubular secretion

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U2 - 10.1016/S0014-5793(99)01221-1

DO - 10.1016/S0014-5793(99)01221-1

M3 - 学術論文

C2 - 10508931

AN - SCOPUS:0032859176

SN - 0014-5793

VL - 459

SP - 128

EP - 132

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -

Functional analysis of rat renal organic anion transporter OAT-K1: Bidirectional methotrexate transport in apical membrane

Abstract

Keywords

ASJC Scopus subject areas

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