Phloretin inhibits Na+ and K+ uptake in cultured alveolar type II cells by reduction of cellular ATP content.

ABSTRACT

A number of Na+ and K+ transport pathways have been identified in the alveolar epithelium and multiple inhibitors have been used to uncover these mechanisms. However, the effect of phloretin, a small dipolar nonelectrolyte compound which exerts many effects on membrane transport on Na+ and K+ uptake in alveolar epithelial cells, is not known. The purpose of this study was then to determine the impact of phloretin in Na+ and K+ uptake in cultured rat alveolar type II cells. Phloretin at a dose of 250 microM decreased Na+ uptake by 80% and K+ uptake by 90%. This decrease in Na+ and K+ uptake was not associated with a cytotoxic effect of phloretin, but this treatment did decrease ATP levels in the cells to 80% of the control cells value by 5 minutes and to 95% by 10 minutes. Our study demonstrates that phloretin is a nonspecific inhibitor of ions transport in alveolar type II cells. This inhibition is probably mediated by a reduction of intracellular ATP content.