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Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1.
- Source :
-
Pharmaceutical research [Pharm Res] 2006 Aug; Vol. 23 (8), pp. 1696-701. - Publication Year :
- 2006
-
Abstract
- Purpose: Transport characteristics and tissue distribution of the rat H+/organic cation antiporter MATE1 (multidrug and toxin extrusion 1) were examined.<br />Methods: Rat MATE1 cDNA was isolated by polymerase chain reaction (PCR) cloning. Transport characteristics of rat MATE1 were assessed by HEK293 cells transiently expressing rat MATE1. The mRNA expression of rat MATE1 was examined by Northern blot and real-time PCR analyses.<br />Results: The uptake of a prototypical organic cation tetraethylammonium (TEA) by MATEI-expressing cells was concentration-dependent, and showed the greatest value at pH 8.4 and the lowest at pH 6.0-6.5. Intracellular acidification induced by ammonium chloride resulted in a marked stimulation of TEA uptake. MATE1 transported not only organic cations such as cimetidine and metformin but also the zwitterionic compound cephalexin. MATE1 mRNA was expressed abundantly in the kidney and placenta, slightly in the spleen, but not expressed in the liver. Real-time PCR analysis of microdissected nephron segments showed that MATE1 was primarily expressed in the proximal convoluted and straight tubules.<br />Conclusions: These findings indicate that MATE1 is expressed in the renal proximal tubules and can mediate the transport of various organic cations and cephalexin using an oppositely directed H+ gradient.
- Subjects :
- Animals
Blotting, Northern
Cells, Cultured
Cloning, Molecular
DNA, Complementary biosynthesis
DNA, Complementary genetics
Humans
Nephrons metabolism
Organic Cation Transporter 1 genetics
Organic Cation Transporter 1 metabolism
Organic Cation Transporter 2
Rats
Reverse Transcriptase Polymerase Chain Reaction
Tissue Distribution
Antiporters genetics
Antiporters metabolism
Organic Cation Transport Proteins genetics
Organic Cation Transport Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0724-8741
- Volume :
- 23
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 16850272
- Full Text :
- https://doi.org/10.1007/s11095-006-9016-3