Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 293, Issue 1, Pages F360-F370Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00102.2007
Keywords
organic cation; transport; tetraethylammonium; proximal tubule; kidney
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Funding
- NIDDK NIH HHS [DK-058251, R01 DK068039] Funding Source: Medline
- NIEHS NIH HHS [ES-06694, K22 ES011646] Funding Source: Medline
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An electroneutral organic cation (OC)/proton exchanger in the apical membrane of proximal tubules mediates the final step of renal OC excretion. Two members of the multidrug and toxin extrusion family, MATE1 and MATE2-K, were recently identified in human and rodent kidney and proposed to be the molecular basis of renal OC/H+ exchange. To take advantage of the comparative value of the large database on the kinetic and selectivity characteristics of OC/H+ exchange that exists for rabbit kidney, we cloned rbMATE1 and rbMATE2-K. The rabbit homologs have 75% (MATE1) and 74% (MATE2-K) amino acid identity to their human counterparts (and 51% identity with each other). rbMATE1 and rbMATE2-K exhibited H+ gradient-dependent uptake and efflux of tetraethylammonium (TEA) when expressed in Chinese hamster ovary cells. Both transporters displayed similar affinities for selected compounds [IC50 values within 2-fold for TEA, 1-methyl-4-phenylpyridinium, and quinidine] and very different affinities for others (IC50 values differing by 8- to 80-fold for choline and cimetidine, respectively). These results indicate that rbMATE1 and rbMATE2-K are multispecific OC/H+ exchangers with similar, but distinct, functional characteristics. Overall, the selectivity of MATE1 and MATE2-K correlated closely with that observed in rabbit renal brush-border membrane vesicles.
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