Molecular identification and functional characterization of rabbit MATE1 and MATE2-K.
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 [IC(50) values within 2-fold for TEA, 1-methyl-4-phenylpyridinium, and quinidine] and very different affinities for others (IC(50) 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.
Zhang
Xiaohong
X
Dept. of Physiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Cherrington
Nathan J
NJ
Wright
Stephen H
SH
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D016466:CHO Cells; D002927:Cimetidine / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D015259:Dopamine Agents / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017433:Protein Structure, Secondary; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D019789:Tetraethylammonium / Q000378:metabolism; D014162:Transfection
D015259:Dopamine Agents; D006635:Histamine H2 Antagonists; D027701:Organic Cation Transport Proteins; D019789:Tetraethylammonium; D002927:Cimetidine; D015655:1-Methyl-4-phenylpyridinium