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

The expression of two members of the ATP-binding cassette family of transpo rt proteins, P-glycoprotein (P-gp) and the canalicular multispecific organi c anion transporter (cMOAT or Mrp2), was evaluated in renal brush-border me mbranes (BBM) and various rat tissues after cisplatin treatment. One admini stration of cisplatin (5 mg/kg) increased P-gp expression by >200-300% in r enal 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 increas ed 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 pr oteins was maximal at 2 days after cisplatin treatment and lasted for at le ast 8 days. These results indicate that a single administration of cisplati n 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.