Organic cation transporter 1, 2, 3 and multidrug and toxin extrusion protein 1, 2-K (OCT/MATE)

The Organic Cation Transporters (OCT1, OCT2, OCT3) and Multidrug and Toxin Extrusion proteins (MATE1, MATE2-K) constitute a coordinated vectorial transport system essential for the disposition of organic cations (UniProt O15245, Q96FL8). OCTs, belonging to the SLC22 family, mediate the electrogenic uptake of substrates from the blood into tissues like the liver and kidney (PMID: 23585110). MATE proteins, belonging to the SLC47 family, function as H+/organic cation antiporters that facilitate the final excretion of these substances into the bile or urine (PMID: 21312325). This system is a primary determinant of the pharmacokinetics and pharmacodynamics of numerous drugs, most notably the antidiabetic metformin and the platinum-based chemotherapeutic cisplatin. OCT2 and MATE1/2-K are particularly critical in the renal proximal tubule, where they work in tandem to clear drugs and endogenous metabolites like creatinine. Inhibition of these transporters by drugs such as cimetidine or dolutegravir can lead to significant drug-drug interactions, often manifesting as increased plasma concentrations of co-administered substrates (FDA 2020). Furthermore, genetic polymorphisms in these transporters are associated with inter-individual variability in drug efficacy and the risk of adverse effects, such as cisplatin-induced nephrotoxicity. Consequently, these transporters are key targets for evaluation during drug development to ensure safety and optimize dosing regimens.

Other names

SLC22A1SLC22A2SLC22A3SLC47A1SLC47A2hOCT1hOCT2hOCT3hMATE1hMATE2-KSolute carrier family 22 member 1Solute carrier family 22 member 2Solute carrier family 22 member 3Solute carrier family 47 member 1Solute carrier family 47 member 2

OCTs (SLC22A1-3) function as electrogenic uniporters that facilitate the diffusion of organic cations into cells down their electrochemical gradient. MATEs (SLC47A1-2) function as H+/organic cation antiporters, utilizing the transmembrane proton gradient to efflux cations from the cytoplasm into the extracellular space, such as the renal tubule lumen or the bile canaliculi (PMID: 23585110, 21312325).