Multidrug Resistance Proteins and Hepatic Transport of Endo- and Xenobiotics

Transporters that use ATP are called ATP-binding cassette (ABC) transporters. One family of ABC transporters that plays a major role in the ability of the liver to eliminate various drugs is the multidrug resistance proteins (MRPs). There are nine cloned genes in the MRP (ABCC) subfamily. Generally, these carriers transport diverse sulfate, glutathione, or glucuronide conjugates of endogenous compounds like estrogen and bilirubin, as well as drugs and toxins. Although all of the MRPs mediate ATP-dependent efflux, their tissue expression and cellular localization vary. MRP2 is most highly expressed in the liver at the canalicular domain and is the primary focus of this chapter. Several in vitro approaches to study drug transport in the liver are discussed. Although these approaches have been described in detail elsewhere, the authors present their own perspectives, with particular emphasis on the baculovirus expression vector system. Additional methods and approaches that are discussed include the choice of animal tissue preparation, expression system to be used, and experimental paradigms, including uptake in membrane vesicles, cell monolayers, and procedures to measure ATPase activity and its relationship to transport.