ATP-dependent transport of glutathione S-conjugates by the multidrug resistance protein MRP1 and its apical isoform MRP2

Chem Biol Interact. 1998 Apr 24:111-112:153-61. doi: 10.1016/s0009-2797(97)00158-0.

Abstract

The membrane proteins mediating the ATP-dependent transport of glutathione S-conjugates and related amphiphilic anions have been identified as the multidrug resistance proteins MRP1 and MRP2. These 190-kDa membrane glycoproteins were cloned in recent years and shown to be unidirectional, ATP-driven, export pumps with an amino acid identity of 49% in humans. MRP1 is detected in the plasma membrane of many cell types, including erythrocytes; whereas MRP2, also termed canalicular MRP (cMRP) or canalicular multispecific organic anion transporter (cMOAT), has been localized to the apical domain of polarized epithelia, such as the hepatocyte canalicular membrane and kidney proximal tubule luminal membrane. Physiologically important substrates of both transporters include glutathione S-conjugates, such as leukotriene C4, as well as bilirubin glucuronides. 17 beta-glucuronosyl estradiol and glutathione disulfide. Both transporters have been associated with multiple drug resistance of malignant tumors because of their capacity to pump drug conjugates and drug complexes across the plasma membrane into the extracellular space. The substrate specificity of MRP1 and MRP2 studied in inside-out oriented membrane vesicles is very different from MDR1 P-glycoprotein. MRP1 and MRP2 may be termed conjugate transporting ATPases, functioning in detoxification and, because of their role in glutathione disulfide export, in the defense against oxidative stress.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Anion Transport Proteins
  • Biological Transport, Active
  • Carrier Proteins / metabolism
  • Drug Resistance, Multiple
  • Glutathione / metabolism*
  • Humans
  • Inactivation, Metabolic
  • Multidrug Resistance-Associated Proteins
  • Mutation
  • Oxidative Stress
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Anion Transport Proteins
  • Carrier Proteins
  • Multidrug Resistance-Associated Proteins
  • Recombinant Proteins
  • Adenosine Triphosphate
  • Glutathione