STUDIES OF THE EFFECT OF BENDROFLUMETHIAZIDE ON SODIUM TRANSPORT AND METABOLISM IN THE TOAD BLADDER

¹ Department of Physiology, University of Kansas Medical Center, Kansas City, Kansas

The effect of bendroflumethiazide (BHFT) on the metabolic processes supporting transepithelial Na transport in the isolated toad bladder has been studied. The thiazide inhibited short-circuit current (SCC) in bladders depleted of endogenous glycogen, inhibited stimulation of SCC by glucose and pyruvate and inhibited SCC supported solely by anaerobic metabolism. The drug does not interfere with glycolysis since it increases lactate accumulation. BHFT, however, did depress O₂ consumption. The effect on lactate accumulation and O₂ consumption also occurred in the absence of Na indicating that the drug has a direct effect on metabolism and may not directly affect the Na transport mechanism. Ouabain, which depresses lactate accumulation and inhibits NaK-activated adenosine triphosphatase, caused the same fractional inhibition of SCC in bladders pretreated with BHFT as in control bladders indicating that the effects of these two inhibitors are quite different. The effects of BHFT and fluoroacetate, an inhibitor of the tricarboxylic acid cycle, on SCC were also additive. The data suggest that BHFT depresses Na transport in the toad bladder by interfering with a step linking glycolysis and aerobic metabolism to Na transport. Interference with this step inhibits aerobic metabolism whether Na is present or absent but does not affect glycolysis.