The drug efflux pump MRP2: regulation of expression in physiopathological situations and by endogenous and exogenous compounds.

Article Details

Citation

Payen L, Sparfel L, Courtois A, Vernhet L, Guillouzo A, Fardel O

The drug efflux pump MRP2: regulation of expression in physiopathological situations and by endogenous and exogenous compounds.

Cell Biol Toxicol. 2002;18(4):221-33.

PubMed ID
12206135 [ View in PubMed
]
Abstract

The multidrug resistance-associated protein 2 (MRP2) is an ATP-binding cassette transporter involved in biliary, renal, and intestinal secretion of numerous organic anions, including endogenous compounds such as bilirubin and exogenous compounds such as drugs and toxic chemicals. Its expression can be modulated in various physiopathological situations, notably being markedly decreased during liver cholestasis and upregulated in some cancerous tissues. In addition, MRP2 levels are altered in hepatocytes in response to hormones such as glucocorticoids and to structurally unrelated drugs such as rifampicin, phenobarbital, ritonavir, and cisplatin. The chemical carcinogen 2-acetylaminofluorene and chemopreventive agents such as oltipraz and sulforaphane also markedly increased MRP2 expression in liver parenchymal cells. Interestingly, most of the chemical inducers of MRP2 act on drug-metabolizing enzymes, indicating a coordinated regulation of these detoxifying proteins; cellular mechanisms involved are, at least partly, common and may be related to nuclear hormone receptors such as the pregnane X receptor. Owing to the major role played by MRP2 in elimination of drugs and endogenous compounds, modulation of its expression may lead to adverse effects or to changes in drug pharmacokinetics.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
NifedipineCanalicular multispecific organic anion transporter 1ProteinHumans
Unknown
Inducer
Details
Pharmaco-transcriptomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
RifampicinApprovedABCC21244
upregulated
Rifampin results in increased expression of ABCC2 mRNA10q24.2