Drug Transporters

Abstract

Drug transporters are membrane proteins. They play a critical role in cellular homeostasis by influx or efflux of nutrients, ions, cellular waste, and environmental toxins. Drug transporters are also involved in the regulation of drug distribution and their bioavailability, transport of compounds across the blood-brain barrier, and hematopoietic stem cell protection from toxins. Functionally, they are classified as influx and efflux transporters. Based on their origin, transporters are classified into two major superfamilies, namely, the ABC (ATP-binding cassette) and the SLC (solute carrier) transporters. Clinically important families in ABC superfamily are ABCB, ABCC, and ABCG. All the members of this family are primary active transporters. Important families of SLC superfamily are OAT, OCT, OCTN, OATP, and MATE. Members of this superfamily are either facilitated transporters, secondary active transporters, or tertiary active transporters. All uptake transporters belong to SLC family and efflux transporters belong to ABC family with an exception of MATE export transporter which belongs to SLC family. Transporters expressed in the small intestine, the liver, and the kidney are of particular importance for drug disposition and drug-drug interactions. The P-glycoprotein (coded by the ABCB1 gene), also known as the MDR1 or ABCB1 transporter, gained much importance because of its propensity to cause multidrug resistance; it is one of the best studied export transporters.