Mammalian MATE (SLC47A) transport proteins: impact on efflux of endogenous substrates and xenobiotics

Abstract

Multidrug and toxin extrusion proteins (MATEs; SLC47A) are mammalian transporters being predominately expressed in the brush-border membrane of proximal tubule epithelial cells in the kidney and the canalicular membrane of hepatocytes. Functionally, MATEs act as efflux transporters for organic compounds, thereby mediating the elimination process. Two isoforms, MATE1 and 2, have been identified, and, so far, only a limited number of substrates, including clinically used drugs such as metformin and cimetidine, are known. A knockout mouse model has been established, as well, and is a valuable tool for further systematic pharmacokinetic analyses. In this review, we summarize the progress in MATE research on structural, molecular, functional, and pathophysiological aspects. Consequences of genetic variants for pharmacokinetic alterations and drug therapy are discussed.

Keywords::

• drug-drug
• interactions
• organic cations
• polymorphisms
• proton antiporter
• SLC47A1
• SLC47A2
• MATE1
• MATE2
• genetic variants
• pharmacogenetics