Physiological, pharmacological and clinical features of the multidrug resistance protein 2.
Multidrug resistance protein 2 (MRP2, ABCC2) is a drug efflux pump belonging to the ATP-binding cassette (ABC) transporter superfamily. MRP2 is present predominantly at the biliary pole of hepatocytes and is also expressed in the kidney and intestine. It plays a major role in hepato-biliary elimination of many structurally diverse xenobiotics, including organic anions and drug conjugates, and therefore most likely contributes to pharmacokinetic parameters of these compounds. MRP2 also handles endogenous molecules such as bilirubin, and its overexpression has been shown to confer a multidrug resistance phenotype to tumoral cells. MRP2 expression can be regulated by endogenous substances such as inflammatory cytokines and biliary acids. The MRP2 levels and activity can also be affected by a large panel of xenobiotics, including chemopreventive agents and ligands of the pregnane X receptor, which may be a potential source of drug-drug interactions and drug adverse effects. MRP2 appears therefore as one of the major drug efflux pumps of the organism, whose functional and regulatory features are important to consider, notably for drug disposition.
Fardel
Olivier
O
Inserm U620, Faculté de Pharmacie, 2 Avenue Professeur Leon Bernard, 35043 Rennes, France. olivier.fardel@univ-rennes1.fr
Jigorel
Emilie
E
Le Vee
Marc
M
Payen
Lea
L
D000818:Animals; D004347:Drug Interactions; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D010599:Pharmacokinetics
D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human