Defense Barriers in the Body:Contribution of Multidrug Resistance-Associated Protein 2

Multidrug resistance-associated protein 2 (MRP2, gene nomenclature ABCC2), a member of the family of ATP-binding cassette (ABC-) transporters, is present in the canalicular membrane of hepatocytes and in the apical membrane of enterocytes and renal tubule epithelial cells. At all of these barriers, MRP2 contributes to reduction of the body load of potentially toxic xenobiotics and endogenous waste products. This important “gatekeeper” function of MRP2 has been recognized recently, and data regarding this function are reviewed here. In its function at these barriers, MRP2 is part of a complex detoxification pathway that is regulated by nuclear receptors as common activators. However, MRP2 also can mediate toxicity by concentrating toxicants in the biliary duct and reducing the bioavailability of protective compounds.