1,25-Dihydroxyvitamin D-stimulated calmodulin binding proteins: a sustained effect on distal tubules

2002 ◽  
Vol 282 (1) ◽  
pp. F77-F84 ◽  
Author(s):  
Emmanuel K. O. Siaw ◽  
Marian R. Walters
Keyword(s):  
Vitamin D ◽  
Time Course ◽  
Binding Proteins ◽  
Day Treatment ◽  
Rat Kidney ◽  
Vitamin D Receptors ◽  
Dihydroxyvitamin D ◽  
Calmodulin Binding ◽  
1,25 Dihydroxyvitamin D

The tubular localization of 1,25-dihydroxyvitamin D[1,25(OH)2D3]-stimulated calmodulin binding proteins (CaMBP-Ds) in the rat kidney and the specificity of their induction were characterized to better understand renal responses to protracted 1,25(OH)2D3 treatment in vivo. None of the other hormones tested (parathyroid hormone, calcitonin, estradiol-17β, testosterone, progesterone, hydrocortisone, or dexamethasone) stimulated the CaMBP-Ds, whereas maximal 1,25(OH)2D3 stimulation occurred after a 5- to 7-day treatment with 100 ng/day 1,25(OH)2D3. With the exception of the more ubiquitously distributed CaMBP-D150, the CaMBP-Ds were localized in distal, but not proximal, tubule preparations. 1,25(OH)2D3 induction of vitamin D receptors and the CaMBP-Ds was similar with respect to dose-response and time course. Finally, the CaMBP-Ds remained elevated for at least 4 wk after 1,25(OH)2D3 withdrawal. Because the vitamin D-stimulated renal CaMBP-Ds are principally proteins of the distal tubule, they may be associated with renal regulation of Ca2+ homeostasis. The sustained induction of CaMBP-Ds is important in addressing the question of whether their induction is a function of normal Ca2+ homeostasis or a pathophysiological consequence of hypervitaminosis D and hypercalcemia.

scholarly journals The Receptor-Dependent Actions of 1,25-Dihydroxyvitamin D Are Required for Normal Growth Plate Maturation in NPt2a Knockout Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4607-4612 ◽  
Author(s):  
Susanne U. Miedlich ◽  
Eric D. Zhu ◽  
Yves Sabbagh ◽  
Marie B. Demay
Keyword(s):  
Vitamin D ◽  
Growth Plate ◽  
Fibroblast Growth Factor 23 ◽  
Normal Growth ◽  
Chondrocyte Apoptosis ◽  
Apoptotic Pathway ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Hypertrophic Chondrocyte

Rickets is a growth plate abnormality observed in growing animals and humans. Rachitic expansion of the hypertrophic chondrocyte layer of the growth plate, in the setting of hypophosphatemia, is due to impaired apoptosis of these cells. Rickets is observed in humans and mice with X-linked hypophosphatemia that is associated with renal phosphate wasting secondary to elevated levels of fibroblast growth factor-23. Rickets is also seen in settings of impaired vitamin D action, due to elevated PTH levels that increase renal phosphate excretion. However, mice with hypophosphatemia secondary to ablation of the renal sodium-dependent phosphate transport protein 2a (Npt2a), have not been reported to develop rickets. Because activation of the mitochondrial apoptotic pathway by phosphate is required for hypertrophic chondrocyte apoptosis in vivo, investigations were undertaken to address this paradox. Analyses of the Npt2a null growth plate demonstrate expansion of the hypertrophic chondrocyte layer at 2 wk of age, with resolution of this abnormality by 5 wk of age. This is temporally associated with an increase in circulating levels of 1,25-dihydroxyvitamin D. To address whether the receptor-dependent actions of this steroid hormone are required for normalization of the growth plate phenotype, the Npt2a null mice were mated with mice lacking the vitamin D receptor or were rendered vitamin D deficient. These studies demonstrate that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for maintenance of a normal growth plate phenotype in the Npt2a null mice.

Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

2008 ◽  
Vol 295 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
Michael S. K. Wong ◽  
R. Delansorne ◽  
Ricky Y. K. Man ◽  
Paul M. Vanhoutte
Keyword(s):  
Vitamin D ◽  
Calcium Concentration ◽  
Free Calcium ◽  
Spontaneously Hypertensive ◽  
Vitamin D Receptors ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
A 23187 ◽  
Free Calcium Concentration ◽  
Cytosolic Free Calcium Concentration

The available evidence suggests that vitamin D has cardiovascular effects besides regulating calcium homeostasis. To examine the effect of 1,25-dihydroxyvitamin D3, the major metabolite of vitamin D, on endothelium-dependent contractions, aortic rings of spontaneously hypertensive rats (SHR) were suspended in organ chambers for isometric force measurements. Rings were incubated with Nω-nitro-l-arginine methyl ester (l-NAME) and then exposed to increasing concentrations of acetylcholine, ATP, or the calcium ionophore to trigger contractions. This was done in the absence or presence of 1,25-dihydroxyvitamin D3. The release of prostacyclin after acetylcholine or A-23187 stimulation was also measured. The cytosolic-free calcium concentration was measured by confocal microscopy after incubation with the fluorescent dyes fluo-4 and fura red. The presence of vitamin D receptors was confirmed using immunohistochemistry. Acetylcholine- and ATP-induced endothelium-dependent contractions were significantly reduced compared with those obtained in the absence of the drug. This effect was not present if A-23187 was used as an agonist. The acetylcholine- but not the A-23187-induced release of prostacyclin was reduced by the acute administration of 1,25-dihydroxyvitamin D3. Exposure to 1,25-dihydroxyvitamin D3 reduced the increase in cytosolic-free calcium concentration caused by acetylcholine but not by A-23187 in cells. Vitamin D receptors were densely distributed in the endothelium. Inecalcitol (19-nor-14-epi-23-yne-1,25-dihydroxyvitamin D3), a synthetic analog of vitamin D, caused a comparable depression of endothelium-dependent contractions as 1,25-dihydroxyvitamin D3. These results demonstrate that vitamin D3 modulates vascular tone by reducing calcium influx into the endothelial cells and hence decreasing the production of endothelium-derived contracting factors.

Uptake of the hormone 1,25-dihydroxyvitamin D3 by the dog liver

1986 ◽  
Vol 64 (6) ◽  
pp. 699-702 ◽  
Author(s):  
Marielle Gascon-Barré ◽  
Sylvie Vallières ◽  
Pierre-Michel Huet
Keyword(s):  
Vitamin D ◽  
Hepatic Clearance ◽  
Hepatic Uptake ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Multiple Indicator Dilution ◽  
Systemic Bioavailability ◽  
Dog Liver

The hepatic uptake of the hormone 1,25-dihydroxyvitamin D3 has been studied, in vivo, using the multiple indicator dilution technique. The fractional uptake of 1,25-dihydroxyvitamin D3 during a single circulatory passage across the dog liver has been estimated at 34.4 ± 3.3% while its hepatic clearance was estimated at 364.3 ± 94.1 mL/min. The hepatic uptake of 1,25-dihydroxyvitamin D3 is discussed in relation to its systemic bioavailability following intravenous or oral administration as well as in relation to the hepatic uptake of other vitamin D sterols; it is postulated that the hepatic uptake of vitamin D sterols does not seem to be mediated by specific receptors on the liver plasma membrane; it seems, however, that the hepatic uptake of vitamin D sterols may be inversely related to their relative affinity for the circulating carrier, the vitamin D binding protein.

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