PHLORHIZIN 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 (N-0) and not to changes in the dissociation constant (K-d) 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. (C) 1995 Academic Press, Inc.