Vanadate inhibits urinary acidification by the turtle bladder

Abstract

We studied the effect of vanadate on urinary acidification by the turtle bladder in vitro. Vanadate added to the serosal, but not to the mucosal, solution caused a dose dependent inhibition of hydrogen ion secretion in short circuited hemibladders in the presence and in the absence of ouabain. The failure of mucosal addition of vanadate to inhibit hydrogen ion secretion was due to the fact that vanadate tissue uptake from the serosal solution was 30 times greater than that from the mucosal solution, suggesting that vanadate must enter the cell to inhibit hydrogen ion secretion. The effect of vanadate on hydrogen ion secretion could not be explained by alterations in calcium uptake of efflux. The effect of vanadate on hydrogen ion secretion under aerobic conditions could not be explained solely by inhibition of mitochondrial function because the relative magnitude of the inhibitory effect of this compound was the same under aerobic and anaerobic conditions. Vanadate caused a significant inhibition of the proton motive force (PMF) without altering backleak of hydrogen ion or bicarbonate secretion. Under anaerobic conditions vanadate inhibited hydrogen ion secretion and caused a significant increase in lactate production without the expected increase in ARP/ADP ratio. ATP levels under anaerobic conditions were not significantly different between control and vanadate treated hemibladders, indicating that limited ATP availability can not explain the inhibitory effect of vanadate on hydrogen ion secretion. These findings indicate that vanadate has a number of effects that are capable of explaining the inhibition of urinary acidification. Among those effects, the inhibition of hydrogen ion secretion and the PMF by vanadate may be due to direct inhibition of the hydrogen ion pump, intereference with ATP utilization by the pump, or other metabolic effects.