Multidrug and toxin extrusion proteins (MATE/SLC47); role in pharmacokinetics

Int J Biochem Cell Biol. 2013 Sep;45(9):2007-11. doi: 10.1016/j.biocel.2013.06.022. Epub 2013 Jul 5.

Abstract

Mammal multidrug and toxin extrusion protein 1 (MATE 1) encoded by SLC47A1 gene was described in 2005 as an efflux transporter that mediates proton-coupled organic cation secretion. Shortly after, other isoforms (MATE2 and MATE2-K, both encoded by SLC47A2 gene) were identified. In the kidney and liver, MATEs work in concert with organic cation transporters (OCTs), together representing an eliminatory pathway for organic cations. Over 40 clinically used drugs and several endogenous compounds are known substrates or inhibitors of MATEs and the list is constantly growing. These transporters are supposed to modulate pharmacokinetics/toxicokinetics and to play a role in drug resistance and (patho)physiological processes. Drug-drug interactions on MATE transporters and polymorphisms in SLC47A genes may affect renal excretion of substrate drugs, such as metformin, resulting in inadequate pharmacotherapy or occurrence of toxic effects. Expression and function of MATEs in tissues other than kidney and liver remain to be elucidated.

Keywords: Drug–drug interactions; Efflux transporter; Multidrug and toxin extrusion; Pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Interactions
  • Humans
  • Kidney / metabolism
  • Liver / metabolism
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism*
  • Pharmacokinetics*
  • Polymorphism, Genetic

Substances

  • Organic Cation Transport Proteins
  • SLC47A1 protein, human
  • SLC47A2 protein, human