, Volume 23, Issue 8, pp 1696-1701
Date: 19 Jul 2006

Molecular Cloning, Functional Characterization and Tissue Distribution of Rat H+/Organic Cation Antiporter MATE1

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Purpose

Transport characteristics and tissue distribution of the rat H+/organic cation antiporter MATE1 (multidrug and toxin extrusion 1) were examined.

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.

Results

The uptake of a prototypical organic cation tetraethylammonium (TEA) by MATE1-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.

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.