Cisplatin interaction with organic cation uptake by opposum kidney (OK) cells

M. R. Escobar, C. Woodland, S. Ito, G. Koren

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One major side-effect limiting the clinical use of the anti-neoplastic agent cisplatin is its nephrotoxicity. Cisplatin is actively accumulated and secreted by the renal tubules possibly via the mechanism that may share that for organic ion renal transport. Interaction of cisplatin with the organic ion transport systems was studied using opposum kidney (OK) cells in culture. Initial rates of uptake of the cation tetraethylammonium (TEA) in the absence and presence (100 μM) of cisplatin were performed. TEA was accumulated by OK cells with an apparent Km of 125±5 μM and an apparent Vmax of 3.3±0.1 nmol/106 cells/hr. Addition of cisplatin did not affect Km (117±6 mu;M, P<0.6) but caused an increase in Vmax (3.7±0.1 nmol/106 cells/hr, P<0.05). An apparent increase in TEA (25 μM) accumulation (maximum of 20%, P<0.03) was observed at all concentrations of cisplatin used (1-100 μM). Studies were also performed with the organic anion para-aminohippurate (PAH) but no interactions with cisplatin were apparent. The present studies suggest a possible cisplatin-TEA interaction in OK cells. Cisplatin may alter the efflux of TEA across the apical membrane and not its influx into the cell at the basolateral membrane.

Original languageEnglish
Pages (from-to)216
Number of pages1
JournalClinical Pharmacology and Therapeutics
Issue number2
StatePublished - 1997
Externally publishedYes


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