MATE transporters: involvement in drug pharmacokinetics and drug-drug interactions

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DOI: https://doi.org/10.29296/25419218-2019-07-08
Issue: 
7
Year: 
2019

V.A. Evteev(1), A.B. Prokofyev(1, 2), N.D. Bunyatyan(1, 2), V.G. Kukes(1) 1-Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation, 8, Petrovsky Boulevard, Build. 2, Moscow 127051, Russian Federation 2-I.M. Sechenov First Moscow State Medical University (Sechenov University), 8, Trubetskaya St., Build. 2, Moscow 119048, Russian Federation

Along with organic cation transporters (OCT) and organic anion transporters (OAT), MATE transporters belong to the solute carrier (SLC) family. They are transmembrane proteins and are located on the apical side of the cell membrane of the liver and kidney. Three human MATE isoforms, namely MATE1, MATE2, and MATE2-K, have been now studied. MATE1 is predominantly expressed in the liver, kidneys, and skeletal muscles. MATE2-K and MATE2 are expressed in the renal proximal tubular epithelial cells and hepatocytes, respectively. All the transporters of this subfamily are distinguishing. The transport mechanism has not yet been fully studied; the transport according to the principle of antiport in exchange for sodium cations (Na+) is currently considered most preferable. The direction of transport is shown to be pH-dependent. The MATE transporters have a broad range of transportable substrates, both endogenous and xenobiotic, mainly organic cations. The key substrates of MATE transporters among drugs are metformin, platinum preparations, acyclovir, cephalosporins, etc. It is worth noting that there is a great similarity to the spectrum of OCT substrates. The MATE transporters located on the apical membrane are most likely to form a functional unit with basolateral OCT transporters. This unit is capable of transporting organic cations through the hepatocyte and renal proximal tubular epithelium. The clinically significant genetic polymorphisms of MATE transporters have not yet been identified now. When drugs and MATE transporter substrates are used simultaneously, there may be a drug-drug interaction, which is manifested by the higher incidence of adverse drug reactions.
Keywords: 
transporters
MATE
metformin
cisplatin
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