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

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Demeule M, Brossard M, Beliveau R

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

Am J Physiol. 1999 Dec;277(6 Pt 2):F832-40.

PubMed ID

10600929 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cisplatin	Canalicular multispecific organic anion transporter 1	Protein	Humans	Unknown	Inducer	Details