The identification of certain members of the large superfamily of ATP bindi
ng cassette transport proteins such as MDRI-P-glycoprotein and the multidru
g resistance protein MRPI as ATP-dependent drug efflux pumps has been a maj
or 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 MDR I, MRPI mainly transports anionic
Phase Il-conjugates. In addition MRP I-mediated drug resistance is highly
dependent on high intracellular glutathione levels which may be linked to t
he apparent physiological involvement of MRPI in glutathione-related cellul
ar processes. This review summarizes the current knowledge about functional
aspects of MRPI and its five recently cloned homologues MRP2-MRP6 and disc
usses their substrate specificities and cellular localization with emphasis
on drug resistance. (C) 2000 Harcourt Publishers Ltd.