Phlorizin binding to renal outer cortical brush-border membranes of cadmium-injected rabbits

The effect of cadmium injection on the high-affinity phlorizin binding to renal outer cortical brush-border membranes was studied in rabbits. Animals received subcutaneous injections of CdCl2 at a dose of 3 mg Cd/kg.day for about 3 weeks. Brush-border membranes were isolated from renal outer cortex by Percoll gradient centrifugation and magnesium precipitation. Cadmium injection resulted in a marked increase in membrane cadmium content and decrease in Na(+)-dependent phlorizin binding. The latter effect was attributed to a reduction in the number of binding sites (N0) and not to changes in the dissociation constant (Kd). Similar results were observed in normal membrane vesicles directly exposed to cadmium in vitro. These results suggest that one mechanism of the cadmium-induced glycosuria is a loss of active Na(+)-glucose cotransport carrier in the proximal tubular brush-border membrane by direct interaction with free cadmium.