Calcitonin inhibits Na+ gradient-dependent phosphate uptake across renal brush-border membranes.

Abstract

This study was undertaken to determine whether calcitonin inhibits Na+-(Pi) cotransport across luminal brush-border membrane (BBM) of proximal tubules. Further, we determined the relative inhibitions of inorganic phosphate (Pi) transport in BBM vesicles (BBMV) derived from superficial cortical tissue (BBMV-SC) and juxtamedullary tissue (BBMV-JM). The effects of maximally phosphaturic doses of calcitonin were compared with those of parathyroid hormone (PTH). Experiments were performed in acutely thyroparathyroidectomized (TPTX) rats fed either normal (NPD, 0.7%) or low (LPD, 0.07%) Pi diets. After measurement of the fractional excretion of phosphate (FEPi) by clearance, the BBMV-SC and BBMV-JM were prepared from kidneys of the same animals and uptakes of 32Pi were determined. Both calcitonin and PTH inhibited BBMV transport of Pi to a greater degree in BBMV-JM than in BBMV-SC, in rats fed NPD or LPD. Kinetic analysis shows that administration of calcitonin resulted in marked decrease of apparent Vmax for Pi without any changes in apparent Km for Pi. However, in spite of a decreased capacity for Na+ gradient-dependent 32Pi uptake in BBMV-JM and much lesser in BBMV-SC in response to administration of calcitonin and PTH in Pi-deprived rats, these phosphaturic peptides did not increase FEPi. We conclude that calcitonin administration decreases the capacity for Na+-Pi cotransport across BBM in proximal tubules of the acutely TPTX rat.