Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2

Satohiro Masuda, Tomohiro Terada, Atsushi Yonezawa, Yuko Tanihara, Koshiro Kishimoto, Toshiya Katsura, Osamu Ogawa, Ken Ichi Inui

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Abstract

A cDNA coding a new H+/organic cation antiporter, human kidney-specific multidrug and toxin extrusion 2 (HMATE2-K), has been isolated from the human kidney. The hMATE2-K cDNA had an open reading frame that encodes a 566-amino acid protein, which shows 94, 82, 52, and 52% identity with the hMATE2, hMATE2-B, hMATE1, and rat MATE1, respectively. Reverse transcriptase-PCR revealed that hMATE2-K mRNA but not hMATE2 was expressed predominantly in the kidney, and hMATE2-B was ubiquitously found in all tissues examined except the kidney. The immunohistochemical analyses revealed that the HMATE2-K as well as the hMATE1 was localized at the brush border membranes of the proximal tubules. HEK293 cells that were transiently transfected with the hMATE2-K cDNA but not hMATE2-B exhibited the H+ gradient-dependent antiport of tetraethylammonium (TEA). Transfection of hMATE2-B had no affect on the hMATE2-K-mediated transport of TEA. hMATE2-K also transported cimetidine, 1-methyl-4-phenylpyridinium (MPP), procainamide, metformin, and N 1-methylnicotinamide. Kinetic analyses demonstrated that the Michaelis-Menten constants for the hMATE2-K-mediated transport of TEA, MPP, cimetidine, metformin, and procainamide were 0.83 mM, 93.5 μM, 0.37 mM, 1.05 mM, and 4.10 mM, respectively. Ammonium chloride-induced intracellular acidification significantly stimulated the hMATE2-K-dependent transport of organic cations such as TEA, MPP, procainamide, metformin, N1- methylnicotinamide, creatinine, guanidine, quinidine, quinine, thiamine, and verapamil. These results indicate that hMATE2-K is a new human kidney-specific H+/organic cation antiporter that is responsible for the tubular secretion of cationic drugs across the brush border membranes.

Original languageEnglish
Pages (from-to)2127-2135
Number of pages9
JournalJournal of the American Society of Nephrology
Volume17
Issue number8
DOIs
Publication statusPublished - Aug 1 2006
Externally publishedYes

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Antiporters
Tetraethylammonium
Cations
Procainamide
Metformin
Kidney
Complementary DNA
Cimetidine
Microvilli
1-Methyl-4-phenylpyridinium
Ammonium Chloride
Quinidine
Quinine
Membranes
HEK293 Cells
Thiamine
Guanidine
Ion Transport
Verapamil
Reverse Transcriptase Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. / Masuda, Satohiro; Terada, Tomohiro; Yonezawa, Atsushi; Tanihara, Yuko; Kishimoto, Koshiro; Katsura, Toshiya; Ogawa, Osamu; Inui, Ken Ichi.

In: Journal of the American Society of Nephrology, Vol. 17, No. 8, 01.08.2006, p. 2127-2135.

Research output: Contribution to journalArticle

Masuda, Satohiro ; Terada, Tomohiro ; Yonezawa, Atsushi ; Tanihara, Yuko ; Kishimoto, Koshiro ; Katsura, Toshiya ; Ogawa, Osamu ; Inui, Ken Ichi. / Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. In: Journal of the American Society of Nephrology. 2006 ; Vol. 17, No. 8. pp. 2127-2135.
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AU - Tanihara, Yuko

AU - Kishimoto, Koshiro

AU - Katsura, Toshiya

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AU - Inui, Ken Ichi

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