Cisplatin induces renal expression of P-glycoprotein and canalicular multispecific organic anion transporter

Am J Physiol. 1999 Dec;277(6):F832-40. doi: 10.1152/ajprenal.1999.277.6.F832.


The expression of two members of the ATP-binding cassette family of transport proteins, P-glycoprotein (P-gp) and the canalicular multispecific organic anion transporter (cMOAT or Mrp2), was evaluated in renal brush-border membranes (BBM) and various rat tissues after cisplatin treatment. One administration of cisplatin (5 mg/kg) increased P-gp expression by >200-300% in renal BBM and in crude membranes from liver and intestine. The increase in P-gp expression in the kidney was also detected in photolabeling experiments, suggesting the induction of functional P-gp. cMOAT expression was increased by >10-fold in renal BBM after cisplatin administration, although it had no effect on liver cMOAT expression. The increase in the levels of both proteins was maximal at 2 days after cisplatin treatment and lasted for at least 8 days. These results indicate that a single administration of cisplatin induces overexpression of P-gp and cMOAT in specific tissues. This may be of significant relevance to the design of clinical trials using cisplatin as a single chemotherapeutic agent or in combination with other drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Animals
  • Anion Transport Proteins
  • Brain / metabolism
  • Capillaries / metabolism
  • Carrier Proteins / genetics*
  • Cell Membrane / metabolism
  • Cerebrovascular Circulation
  • Cisplatin / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Microvilli / metabolism
  • Organ Specificity
  • Rats
  • Rats, Sprague-Dawley


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anion Transport Proteins
  • Carrier Proteins
  • Cisplatin