Effect of cisplatin on organic ion transport in membrane vesicles from rat kidney cortex.
Purified renal membrane vesicles were utilized to gain indirect information regarding the renal handling of cisplatin. The effects of cisplatin on prototypical organic anion (p-amino-hippurate, PAH) and cation (N1-methylnicotinamide; tetraethylammonium, TEA) transport in brush border and basolateral membrane vesicles prepared from rat kidney cortex were observed. While cisplatin inhibited organic cation transport (N1-methylnicotinamide; TEA) in brush border and basolateral membranes, no interaction with the organic anion (p-amino-hippurate) system was observed. Kinetic analyses revealed that cisplatin is a competitive inhibitor of TEA transport in brush border membranes with a ki of 0.12 mM. While the relationship between organic cation transport inhibition and cisplatin nephrotoxicity is unknown, it may suggest that the cisplatin complex itself is transported into the kidney by the organic cation system. The reported effect of the organic anion, probenecid, on the renal handling of cisplatin is discussed in light of these results.
Williams
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Hottendorf
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000201:enzymology / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D013757:Tetraethylammonium Compounds; D009536:Niacinamide; D019789:Tetraethylammonium; D002945:Cisplatin; C024058:N(1)-methylnicotinamide; D010130:p-Aminohippuric Acid