25-Hydroxycholecalciferol and 1,25-dihydroxycholecalciferol enhances phosphaturia in rats with reduced renal mass: evidence for a PTH-dependent mechanism.
To evaluate the acute effect of 25-hydroxycholecalciferol [25(OH)D3] on renal handling of phosphate in rats with reduced renal mass, clearance studies were performed in the following groups of five sixth (5/6) nephrectomized (NPX) animals: (1) rats with intact parathyroids infused 25(OH)D3 (5/6 NPX + 25(OH)D3), (2) rats with intact parathyroids which received the vitamin D vehicle only (5/6 NPX). A separate subgroup of animals received 1,25-dihydroxycholecalciferol [1,25(OH)2D3] [5/6 NPX + 1,25(OH)2D3], (3) parathyroidectomized (PTX) rats infused 25(OH)D3 [5/6 NPX-PTX + 25(OH)D3], and (4) PTX rats infused the vehicle only (5/6 NPX-PTX). In group 1 [5/6 NPX + 25(OH)D3] the final fractional excretion of phosphate (CP/CIn) was significantly higher, i.e., 0.281 +/- 0.016, as compared to that of control animals (group 2, 5/6 NPX) in which the final CP/CIn averaged 0.195 +/- 0.016 (p less than 0.005). There was no difference, however, in the urinary cAMP excretion between these two groups. A similar phosphaturic effect was seen in rats infused 1,25(OH)2D3. After parathyroidectomy, however, the final CP/CIn was similar in rats receiving 25(OH)D3 [group 3, 5/6 NPX-PTX + 25(OH)D3] and in those receiving the vehicle alone (group 4, 5/6 NPX-PTX). In vitro studies on renal cortical adenylate cyclase activity in kidney remnants from the rats with reduced renal mass failed to demonstrate blunting of PTH activation of the enzyme by 25(OH)D3 or by 1,25(OH)2D3 as seen in kidneys from the control intact animals. These experiments demonstrate a phosphaturic response to 25(OH)D3 without parallel change in urinary cAMP in 5/6 NPX with intact parathyroids.(ABSTRACT TRUNCATED AT 250 WORDS)
Rubinger
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Nephrology Services, Hadassah University Hospital, Jerusalem, Israel.
Wald
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Popovtzer
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002112:Calcifediol / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000652:urine; D004789:Enzyme Activation; D005919:Glomerular Filtration Rate; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016105:Parathyroidectomy; D010710:Phosphates / Q000652:urine*; D010760:Phosphorus Metabolism Disorders / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains
D010281:Parathyroid Hormone; D010710:Phosphates; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002117:Calcitriol; D002112:Calcifediol