Uncoupling of Na+-dependent solute transport in renal brush border membranes of maleate-treated rats.

The effect of maleate on the Na+-dependent transport of glucose, phenylalanine and phosphate in the renal brush border membranes (BBM) was studied. It was found that maleate as such had no effect on the isolated BBM vesicles. In BBM isolated from kidney cortex slices which were incubated with maleate, as well as in BBM isolated from the kidneys of maleate-treated rats, an inhibition of the Na+-dependent glucose and phenylalanine transport was observed, whereas the Na+-dependent phosphate transport was stimulated. In kidney slices these effects were prevented by the simultaneous addition of acetoacetate to the incubation medium. The permeability to Na+ ions was increased in the brush border membranes isolated from maleate-treated renal tissue. Cyclic AMP level was decreased nearly by half in the kidneys of maleate-treated rats. It is concluded that the formation of maleyl-CoA, which is prevented by acetoacetate, is a prerequisite for the effects of maleate on the BBM. The data suggest that the inhibition of Na+-dependent glucose and phenylalanine transport results from the uncoupling of Na+ and solute transport, due to increased permeability of the BBM to Na+. The stimulation of the phosphate transport system results probably from a decrease of cell cyclic AMP level. It is suggested that the uncoupling of Na+ and solute transport in the BBM is responsible for the generalized impairment by maleate of solute reabsorption in the renal proximal tubules.