Troglitazone stimulates basolateral rheogenic Na+/HCO3- cotransport activity in rabbit proximal straight tubules

Experimental Nephrology
S MutoY Asano

Abstract

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 microM 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 HCO3- in the absence and presence of Tro. The apparent transference number of HCO3- (tHCO3), as calculated from the V(B) deflection, was significantly greater in the presence of Tro (50 microM) 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 effe...Continue Reading

Citations

Mar 29, 2008·Metabolic Syndrome and Related Disorders·Sunil AsnaniVivian A Fonseca
Dec 16, 2010·Clinical and Experimental Pharmacology & Physiology·Usha PanchapakesanSonia Saad
Nov 11, 2003·Current Medical Research and Opinion·Sunil AsnaniVivian Fonseca
Feb 22, 2002·Current Opinion in Nephrology and Hypertension·Willa A Hsueh, Susanne B Nicholas
Aug 1, 2015·American Journal of Physiology. Renal Physiology·Mary E HandlogtenI David Weiner
Sep 21, 2013·Development·Daniel C BerryJonathan M Graff
May 20, 2021·Cardiovascular Diabetology·Lorenzo NestiAndrea Natali
Dec 18, 2003·The American Journal of Medicine·Vivian Fonseca

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