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Molecular identification and functional characterization of rabbit MATE1 and MATE2
Author(s) -
Zhang Xiaohong,
Wright Stephen H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a909-c
Subject(s) - extracellular , intracellular , kidney , tetraethylammonium , cimetidine , chemistry , affinities , gene isoform , quinidine , biology , pharmacology , biochemistry , microbiology and biotechnology , endocrinology , potassium , gene , organic chemistry
An electroneutral organic cation‐proton exchanger in the apical membrane of proximal tubules mediates the final step of renal organic cation (OC) excretion. Two members of the Multidrug And Toxin Extrusionfamily, MATE1 and MATE2, 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 database on OC/H + exchange in rabbit kidney, we cloned rbMATE1 and rbMATE2. The rabbit isoforms have 75% (MATE1) and 74% (MATE2) amino acid identity to their human counterparts (and 51% identity with each other). The C‐terminus of rbMATE1 is extracellular (vs. intracellular for mMATE1) consistent with 13 membrane helices for the rabbit – and human – MATE1. Rabbit MATE1 and MATE2 both exhibited H + gradient–dependent uptake and efflux of tetraethylammonium (TEA) when expressed in CHO cells, and displayed similar affinities for selected compounds (IC 50 s within 2‐fold for TEA, MPP and quinidine); and very different affinities for others (IC 50 s differing by 8 to 80‐fold for choline and cimetidine). These results indicate that rbMATE1 and rbMATE2 are polyspecific OC/H + exchangers with similar, but distinct functional characters. (DK58251)