Phloretin inhibits Na+ and K+ uptake in cultured alveolar type II cells by reduction of cellular ATP content.
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.
Centre de Recherche, Hôtel-Dieu du CHUM, Montréal, Québec, Canada.
G
G
Skriabin
S
S
Orlov
C
C
Massé
Y
Y
Berthiaume
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010693:Phloretin / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D000255:Adenosine Triphosphate; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D011188:Potassium; D010693:Phloretin