title: The (patho)physiological functions of the MRP family.
abstract: The identification of certain members of the large superfamily of ATP binding cassette transport proteins such as MDR1 -P-glycoprotein and the multidrug resistance protein MRP1 as ATP-dependent drug efflux pumps has been a major contribution in our understanding of the multidrug resistance phenotype of cancer cells. Importantly, both transport proteins that exhibit only low structural homology have a very different substrate specificity but confer resistance to a similar spectrum of natural product chemotherapeutic drugs. In contrast to the drug transporter MDR1, MRP1 mainly transports anionic Phase II-conjugates. In addition MRP1-mediated drug resistance is highly dependent on high intracellular glutathione levels which may be linked to the apparent physiological involvement of MRP1 in glutathione-related cellular processes. This review summarizes the current knowledge about functional aspects of MRP1 and its five recently cloned homologues MRP2-MRP6 and discusses their substrate specificities and cellular localization with emphasis on drug resistance. Copyright 2000 Harcourt Publishers Ltd.
authors.affiliation: Groningen University Institute of Drug Exploration (GUIDE), Department of Gastroenterology, Hepatology, Department of Medical Oncology, University Hospital Groningen, Groningen, The Netherlands
authors.forename: Johan
authors.initials: J
authors.lastname: Renes
authors.forename: Elisabeth G. E.
authors.initials: EG
authors.lastname: de Vries
authors.forename: Peter L. M.
authors.initials: PL
authors.lastname: Jansen
authors.forename: Michael
authors.initials: M
authors.lastname: Müller