Cisplatin-induced changes in sodium, chloride, and urea transport by the frog skin

Cisplatin is a platinum-containing antitumor agent whose usefulness is limited by nephrotoxicity. We examined the effects of cisplatin on a representative, transporting epithelium--the frog skin. Cisplatin (10(-3)M) from the mucosal surface increased the active transport of sodium by 35 to 40%, as monitored by short-circuit current. The cisplatin-induced increase in short-circuit current was inhibited by amiloride and was additive to the effects of vasopressin (20 mU/ml of serosal solution). Cisplatin from the mucosal surface also decreased transeptithelial electrical resistance by about 35% and increased the permeability to sodium, chloride, and urea. None of these effects of cisplatin occurred with platinum sulfate, platinum chloride, or the trans-isomer of cisplatin. Accordingly, we conclude that cisplatin increases the permeability of the mucosal surface of the frog skin to sodium, chloride, and urea and that these changes are related to the cis-configuration of the drug rather than simply its heavy metal moiety.