Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics
Abstract
The renal organic cation transport system mediates the tubular secretion of cationic compounds including drugs, toxins and endogenous metabolites into urine. It consists of a membrane potential-dependent organic cation transporter at the basolateral membrane and an H(+) /organic cation antiporter at the brush-border membrane. In 2005, human multidrug and toxin extrusion MATE1/SLC47A1 was identified as a mammalian homologue of bacterial NorM. Thereafter, human MATE2-K/SLC47A2 and rodent MATE were found. Functional characterization revealed that MATE1 and MATE2-K were H(+) /organic cation antiporter, mediating the renal tubular secretion of cationic drugs in cooperation with the basolateral organic cation transporter OCT2. Recently, substrate specificity, transcription mechanisms, structure, polymorphisms, in vivo contributions and clinical outcomes on MATE have been investigated intensively. In this review, we summarize recent findings on MATE1/SLC47A1 and MATE2-K/SLC47A2 and discuss the importance of these transporters to the pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics of cationic drugs.
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