Vitamin D reduces renal NaPi-2 in PTH-infused rats: complexity of vitamin D action on renal P-i handling

Acute administration of dihydroxycholecalciferol [1,25(OH)(2)D-3] blunts ph osphaturia and increases urinary cAMP excretion in parathyroid hormone (PTH )-infused parathyroidectomized (PTX) rats. Because chronic administration o f 1,25(OH)(2)D-3 enhances the phosphaturic response to exogenous parathyroi d hormone despite blunting of urinary cAMP excretion, we have examined the expression of the renal cortex type II Na-Pi cotransporter (NaPi-2) mRNA an d protein in 1) chronic PTX Sabra rats, 2) PTX rats receiving a physiologic al dose of 1,25(OH)2-D-3, 3) PTX rats receiving 35 ng/h of PTH, and 4) rats receiving both PTH and 1,25(OH)(2)D-3, for 7 days via osmotic minipumps. O ur results confirm that there is increased phosphaturia in the PTH+1,25(OH) (2)D-3-infused animals despite blunting of urinary cAMP excretion, a reduce d filtered load of phosphate, and lack of a phosphaturic effect by 1,25(OH) (2)D-3 alone. Both PTH and 1,25(OH)(2)D-3 significantly reduced expression of renal cortex NaPi-2 mRNA and NaPi-2 protein, and the administration of P TH together with 1,25(OH)(2)D-3 had additive effects in further decreasing NaPi-2 mRNA and NaPi-2 protein levels. Expression of two other epithelial t ransporters, type 1 Na-sulfate and type 1 Na-glucose cotransporters, were n ot different between the groups, suggesting specificity of the effects of P TH and 1,25(OH)(2)D-3 on phosphate transport. The effect of chronic adminis tration of 1,25(OH)(2)D-3 has not been noted previously, and the cellular m echanisms and signaling processes that mediate the decrease in NaPi-2 remai n to be determined.