Calcium and renal adaptation to a phosphate load in the thyroparathyroidectomized rat

Infusion of phosphate into thyroparathyroidectomized rats on a normal phosphorus diet caused a decrease in net phosphate reabsorption, even though the plasma concentration of phosphate continued to rise. This response was expressed at the level of the proximal tubule brush-border membrane and was coincident with a decrease in sodium-dependent phosphate uptake in membrane vesicles. Kinetic experiments indicated that the increased phosphate load caused a decrease in the Vmax of the membrane uptake system with no change in the apparent Km for phosphate. The infusion of phosphate resulted in a lowered plasma calcium concentration, and it was previously hypothesized that the inhibition of maximal phosphate reabsorption was mediated by the hypocalcemia. When the fall in plasma calcium was prevented by the simultaneous infusions of calcium and phosphate, the reduction in maximal phosphate reabsorption was blunted; however, the phosphate infusion-induced inhibition of brush-border membrane vesicle phosphate uptake was still evident. Thus a major discrepancy was found to the general concept that renal phosphate reabsorption in vivo correlated positively with sodium-dependent phosphate uptake activity in proximal tubule brush-border membrane vesicles. Several possible explanations to account for this anomaly were discussed. It was also found that calcium infusion into saline-infused thyroparathyroidectomized rats slightly increased maximal phosphate reabsorption but did not affect phosphate uptake in the membrane vesicles.