Troglitazone stimulates basolateral rheogenic Na+/HCO-3 cotransport activity in rabbit proximal straight tubules

Thiazolidinedione derivatives, new insulin-sensitizing antidiabetic agents, are expected to have potential clinical use. Since These drugs cause edema in a variable proportion of patients, we examined whether troglitazone (Tro) has direct action on Na+ transport of rabbit proximal straight tubule perfused in vitro. For this purpose, we measured basolateral membrane voltage (V-B) by conventional microelectrode techniques and intracellular pH (pH(i)) by microscopic fluorescence spectrophotometry with a pH-sensitive fluorescent dye, 2 ' ,7 ' -bis-2-carboxyethyl-5-carboxyfluorescein. Tro at 50 muM in the bath significantly depolarized both transepithelial voltage and V-B. To examine whether the basolateral rheogenic Na+/HCO3- cotransport activity is affected by Tro, we observed V-B deflection upon abrupt 10-fold decrease in bath HCO; in the absence and presence of Tro. The apparent transference number of HCO3-(t(HCO3)), as calculated from the V-B deflection, was significantly greater in the presence of Tro (50 muM) than that seen in its absence. Tro caused cell acidification and increased the intracellular acidification rates (dpH(i)/dt) upon abrupt 10-fold decreases in bath HCO3- and Na+ concentrations. The stimulatory effects of Tro on t(HCO3) and dpH(i)/dt were dose dependent between 5 and 50 muM, but they were unaffected at 0.5 muM. From these results, we conclude that Tro acts on the proximal straight tubule and stimulates the basolateral rheogenic Na+/HCO3- cotransport activity. The stimulatory action of Tro may partly account for edema formation. Copyright (C) 2001 S. Karger AG, Basel.