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Renal type II Na/Pi-cotransporter is strongly imapired in cadmium-treated rats

RENAL TYPE II Na/Pi-COTRANSPORTER IS STRONGLY IMPAIRED IN CADMIUM-TREATED RATS Herak-Kramberger, C.M., B. Spindler, J. Biber, H. Murer and I. Sabolic: IMI, Zagreb, Croatia, and Institute of Physiology, Univ. Zurich, Switzerland The cellular mechanisms of cadmium (Cd) nephrotoxicity are poorly understood. In this study we investigated cellular causes of the Cd-induced phosphaturia in rat. Compared to controls, Cd-treated rats (2 mg Cd/kg B.W., s.c. for 14 days) showed a marked polyuria and phosphaturia. As studied by the rapid filtration technique in isolated cortical brush-border membrane vesicles (BBMV), Na+ gradient-driven uptake of phosphate (32Pi) and of 3H-glucose were markedly decreased in Cd-treated rats, whereas uptake of sulphate (35S) remained unchanged. By Western blotting of BBMV proteins and by indirect immunocytochemistry in 4 um frozen fixed kidney sections, using an antibody against the type II Na/Pi-cotransporter (NaPi-2), we found a diminished expression of this protein in brush-border membrane from Cd-treated rats. However, the expression of water channel aquaporin 1, estimated from the specific antibody staining in brush-border membranes, remained unchanged by Cd. Northern blot analysis showed a strong reduction of 2.7 kb NaPi-2-related mRNA in Cd-affected kidneys. Our data indicate that (a) Cd may reduce reabsorption of Pi in proximal tubules by affecting the expression of the functional Na/Pi-cotransporters in the luminal membrane, and (b) Cd effects on brush-border transporters are selective.

Na/Pi-cotransporter; phosphaturia; cadmium; kidney; rat

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