Function and regulation of multidrug resistance proteins (MRPs) in the renal elimination of organic anions.
The reabsorptive and excretory capacity of the kidney has an important influence on the systemic concentration of drugs. Multidrug resistance proteins (MRP/ABCC) expressed in the kidney play a critical role in the tubular efflux of a wide variety of drugs and toxicants, and, in particular, of their negatively charged phase II metabolites. Nine structurally and functionally related MRP family members have been identified (MRP1-9), which differ from each other by their localization, expression levels, and substrate specificity. During altered physiological circumstances, adaptations in these transporters are required to avoid systemic toxicity as well as renal tubular damage. Key players in these events are hormones, protein kinases, nuclear receptors, and disease conditions, which all may affect transporter protein expression levels. This review discusses current knowledge on the renal characteristics of MRP1-9, with specific focus on their regulation.
van de Water
Femke M
FM
Department of Pharmacology and Toxicology 233, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Masereeuw
Rosalinde
R
Russel
Frans G M
FG
D000818:Animals; D000838:Anions / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000145:classification / Q000502:physiology*; D009930:Organic Chemicals / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D000838:Anions; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009930:Organic Chemicals