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Am J Physiol Renal Physiol 277: F832-F840, 1999;
0363-6127/99 $5.00
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Vol. 277, Issue 6, F832-F840, December 1999

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

Michel Demeule, Mathieu Brossard, and Richard Béliveau

Laboratoire de Médecine Moléculaire, Département de Chimie-Biochimie, Université du Québec à Montréal, Montreal, Quebec H3C 3P8; and Hôpital Sainte-Justine, Montreal, Quebec, Canada H3T 1C5

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.

multidrug resistance; Mrp2; renal brush-border membranes


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