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 phosphaturia and increases urinary cAMP excretion in parathyroid hormone (PTH)-infused parathyroidectomized (PTX) rats. Because chronic administration of 1,25(OH)(2)D(3) enhances the phosphaturic response to exogenous parathyroid hormone despite blunting of urinary cAMP excretion, we have examined the expression of the renal cortex type II Na-P(i) cotransporter (NaPi-2) mRNA and protein in 1) chronic PTX Sabra rats, 2) PTX rats receiving a physiological 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. Our 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 reduced 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 PTH 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 transporters, type 1 Na-sulfate and type 1 Na-glucose cotransporters, were not different between the groups, suggesting specificity of the effects of PTH and 1,25(OH)(2)D(3) on phosphate transport. The effect of chronic administration of 1,25(OH)(2)D(3) has not been noted previously, and the cellular mechanisms and signaling processes that mediate the decrease in NaPi-2 remain to be determined.
Friedlaender
M M
MM
Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel 91120. fried@cc.huji.ac.il
Wald
H
H
Dranitzki-Elhalel
M
M
Zajicek
H K
HK
Levi
M
M
Popovtzer
M M
MM
D000818:Animals; D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D000242:Cyclic AMP / Q000652:urine; D005786:Gene Expression Regulation / Q000187:drug effects; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007672:Kidney Cortex / Q000502:physiology; D008297:Male; D016105:Parathyroidectomy; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D019379:Teriparatide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D002352:Carrier Proteins; D010710:Phosphates; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D019379:Teriparatide; D000242:Cyclic AMP; D002117:Calcitriol