Cav1.3 does not contribute to active 1,25D‐regulated intestinal Ca absorption

The intestinal absorption of calcium (Ca) has been shown to depend on vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and dietary phosphorus (P) concentration. This study was designed to evaluate the role of dietary P independent of vitamin D3 or 1,25(OH)2D3. Vitamin D-deficient rats were studied during dietary P restriction and were compared with control groups raised on a normal-phosphorus diet (NP). Balance studies were sued. Net intestinal Ca absorption was significantly lower with dietary P restriction compared with the NP group. This malabsorption of Ca was corrected by the administration of either D3 for 1,25(OH)2D3, despite hypophosphatemia. Everted gut sacs showed a marked reduction in the uptake of 45Ca in the duodenum, jejunum, and ileum during dietary P restriction. We concluded that dietary P concentration plays a major role in intestinal Ca absorption in the vitamin D-deficient rats. These findings suggest an effect of the low-phosphate diet on the vitamin D-dependent, Ca-transport mechanism.

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Dietary and pharmacological compounds altering intestinal calcium absorption in humans and animals

Nutrition Research Reviews ◽

10.1017/s0954422415000050 ◽

2015 ◽

Vol 28 (2) ◽

pp. 83-99 ◽

Cited By ~ 25

Author(s):

Vanessa Areco ◽

María Angélica Rivoira ◽

Valeria Rodriguez ◽

Ana María Marchionatti ◽

Agata Carpentieri ◽

...

Keyword(s):

Health Professionals ◽

Redox State ◽

Calcium Absorption ◽

Human Cancer ◽

Protein Composition ◽

Dietary Lipids ◽

The Body ◽

Renal Lithiasis ◽

Important Health ◽

Intestinal Ca Absorption

AbstractThe intestine is the only gate for the entry of Ca to the body in humans and mammals. The entrance of Ca occurs via paracellular and intracellular pathways. All steps of the latter pathway are regulated by calcitriol and by other hormones. Dietary and pharmacological compounds also modulate the intestinal Ca absorption process. Among them, dietary Ca and P are known to alter the lipid and protein composition of the brush-border and basolateral membranes and, consequently, Ca transport. Ca intakes are below the requirements recommended by health professionals in most countries, triggering important health problems. Chronic low Ca intake has been related to illness conditions such as osteoporosis, hypertension, renal lithiasis and incidences of human cancer. Carbohydrates, mainly lactose, and prebiotics have been described as positive modulators of intestinal Ca absorption. Apparently, high meat proteins increase intestinal Ca absorption while the effect of dietary lipids remains unclear. Pharmacological compounds such as menadione,dl-butionine-S,R-sulfoximine and ursodeoxycholic acid also modify intestinal Ca absorption as a consequence of altering the redox state of the epithelial cells. The paracellular pathway of intestinal Ca absorption is poorly known and is under present study in some laboratories. Another field that needs to be explored more intensively is the influence of the gene × diet interaction on intestinal Ca absorption. Health professionals should be aware of this knowledge in order to develop nutritional or medical strategies to stimulate the efficiency of intestinal Ca absorption and to prevent diseases.

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Effects of 25-hydroxyvitamin D3 on localisation and extent of gastrointestinal calcium absorption in dairy cattle

Animal Production Science ◽

10.1071/an14344 ◽

2014 ◽

Vol 54 (9) ◽

pp. 1394 ◽

Cited By ~ 5

Author(s):

V. Oehlschlaeger ◽

M. Wilkens ◽

B. Schroeder ◽

S. Daenicke ◽

G. Breves

Keyword(s):

Calcium Absorption ◽

Control Diet ◽

Beneficial Effects ◽

Lactating Cows ◽

Phosphorus Absorption ◽

Underlying Mechanisms ◽

Bone Minerals ◽

Dietary Treatments ◽

Intestinal Ca Absorption ◽

Ca Homeostasis

The combination of 25-hydroxyvitamin D3 (25-OHD3) and a diet negative in dietary cation anion difference (DCAD) has recently been shown to have beneficial effects on peripartal calcium (Ca) homeostasis in dairy cows. To further elucidate the underlying mechanisms, it was the aim of the experiments to investigate the effects of 25-OHD3 in combination with DCAD values about –70 meq/kg DM on pre-duodenal and overall gastrointestinal Ca absorption. A group of six ruminally fistulated lactating cows equipped with a cannula in the proximal duodenum were assigned to three dietary treatments (Control diet, anionic salts, anionic salts +25-OHD3) of 5 weeks each. Urine and faeces were collected quantitatively and flow of duodenal contents was calculated by applying chromium oxide. Blood samples were taken at regular intervals. Treatment with anionic salts and 25-OHD3 resulted in an increased Ca net absorption from the total gastrointestinal tract, which was mainly due to respective increases in intestinal Ca absorption. Furthermore, anionic salts and 25-OHD3-treated animals had significantly higher plasma phosphate concentrations and lower plasma levels of CrossLaps and the overall net absorption of phosphorus was significantly higher in these animals. From these data, it can be concluded that anionic salts in combination with 25-OHD3 positively influence the overall net Ca and phosphorus absorption, which is obviously associated with a reduced mobilisation of bone minerals as indicated by decreases in plasma CrossLaps concentrations.

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Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.1.70 ◽

1995 ◽

Vol 78 (1) ◽

pp. 70-75 ◽

Cited By ~ 12

Author(s):

M. Navidi ◽

I. Wolinsky ◽

P. Fung ◽

S. B. Arnaud

Keyword(s):

Bone Mineral ◽

Mineral Content ◽

Endocrine System ◽

Urinary Calcium ◽

Dietary Salt ◽

Lower Growth ◽

Dihydroxyvitamin D ◽

Body Weights ◽

Intestinal Ca Absorption ◽

Normal Calcium

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% C (LoCa). Final body weights were 9–11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNa diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11–18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absorption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

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1α-Hydroxylase gene ablation and Pi supplementation inhibit renal calcification in mice homozygous for the disrupted Npt2a gene

AJP Renal Physiology ◽

10.1152/ajprenal.00362.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. F675-F681 ◽

Cited By ~ 27

Author(s):

Harriet S. Tenenhouse ◽

Claude Gauthier ◽

Hien Chau ◽

René St.-Arnaud

Keyword(s):

Brush Border Membrane ◽

Elevated Serum ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

Gene Ablation ◽

Renal Brush Border Membrane ◽

25 Hydroxyvitamin D ◽

Intestinal Ca Absorption ◽

Renal Brush Border

Disruption of the major renal Na-phosphate (Pi) cotransporter gene Npt2a in mice leads to a substantial decrease in renal brush-border membrane Na-Pi cotransport, hypophosphatemia, and appropriate adaptive increases in renal 25-hydroxyvitamin D3-1α-hydroxylase (1αOHase) activity and the serum concentration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D]. The latter is associated with increased intestinal Ca absorption, hypercalcemia, hypercalciuria, and renal calcification in Npt2- /- mice. To determine the contribution of elevated serum 1,25(OH)2D levels to the development of hypercalciuria and nephrocalcinosis in Npt2- /- mice, we examined the effects of 1α OHase gene ablation and long-term Pi supplementation on urinary Ca excretion and renal calcification by microcomputed tomography. We show that the urinary Ca/creatinine ratio is significantly decreased in Npt2- /- /1α OHase- /- mice compared with Npt2- /- mice. In addition, renal calcification, determined by estimating the calcified volume to total renal volume (CV/TV), is reduced by ∼80% in Npt2- /- /1α OHase- /- mice compared with that in Npt2- /- mice. In Npt2- /- mice derived from dams fed a 1% Pi diet and maintained on the same diet, we observed a significant decrease in urinary Ca/creatinine that was also associated with ∼80% reduction in CV/TV when compared with counterparts fed a 0.6% diet. Taken together, the present data demonstrate that both 1α OHase gene ablation and Pi supplementation inhibit renal calcification in Npt2- /- mice and that 1,25(OH)2D is essential for the development of hypercalciuria and nephrocalcinosis in the mutant strain.

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Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet

AJP Renal Physiology ◽

10.1152/ajprenal.00680.2013 ◽

2014 ◽

Vol 306 (9) ◽

pp. F1081-F1087 ◽

Cited By ~ 6

Author(s):

Kevin K. Frick ◽

John R. Asplin ◽

Christopher D. Culbertson ◽

Ignacio Granja ◽

Nancy S. Krieger ◽

...

Keyword(s):

Vitamin D ◽

Bone Density ◽

Bone Resorption ◽

Mrna Expression ◽

Kidney Stones ◽

Sprague Dawley ◽

Vitamin D Receptors ◽

Low Calcium Diet ◽

Renal Tubular ◽

Intestinal Ca Absorption

Genetic hypercalciuric stone-forming (GHS) rats demonstrate increased intestinal Ca absorption, increased bone resorption, and reduced renal tubular Ca reabsorption leading to hypercalciuria and all form kidney stones. GHS have increased vitamin D receptors (VDR) at these sites of Ca transport. Injection of 1,25(OH)2D3 (1,25D) leads to a greater increase in urine (u)Ca in GHS than in control Sprague-Dawley (SD), possibly due to the additional VDR. In GHS the increased uCa persists on a low-Ca diet (LCD) suggesting enhanced bone resorption. We tested the hypothesis that LCD, coupled to inhibition of bone resorption by alendronate (alen), would eliminate the enhanced 1,25D-induced hypercalciuria in GHS. SD and GHS were fed LCD and half were injected daily with 1,25D. After 8 days all were also given alen until euthanasia at day 16. At 8 days, 1,25D increased uCa in SD and to a greater extent in GHS. At 16 days, alen eliminated the 1,25D-induced increase in uCa in SD. However, in GHS alen decreased, but did not eliminate, the 1,25D-induced hypercalciuria, suggesting maximal alen cannot completely prevent the 1,25D-induced bone resorption in GHS, perhaps due to increased VDR. There was no consistent effect on mRNA expression of renal transcellular or paracellular Ca transporters. Urine CaP and CaOx supersaturation (SS) increased with 1,25D alone in both SD and GHS. Alen eliminated the increase in CaP SS in SD but not in GHS. If these results are confirmed in humans with IH, the use of bisphosphonates, such as alen, may not prevent the decreased bone density observed in these patients.

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Effects of bisphenol A administration to pregnant mice on serum Ca and intestinal Ca absorption

Animal Science Journal ◽

10.1111/j.1740-0929.2011.00947.x ◽

2011 ◽

Vol 83 (3) ◽

pp. 232-237 ◽

Cited By ~ 7

Author(s):

Hinako OTSUKA ◽

Miki SUGIMOTO ◽

Shuntaro IKEDA ◽

Shinichi KUME

Keyword(s):

Bisphenol A ◽

Pregnant Mice ◽

Intestinal Ca Absorption

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1,25(OH)2D3-enhanced hypercalciuria in genetic hypercalciuric stone-forming rats fed a low-calcium diet

AJP Renal Physiology ◽

10.1152/ajprenal.00296.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. F1132-F1138 ◽

Cited By ~ 14

Author(s):

Kevin K. Frick ◽

John R. Asplin ◽

Nancy S. Krieger ◽

Christopher D. Culbertson ◽

Daniel M. Asplin ◽

...

Keyword(s):

Bone Resorption ◽

Bone Cells ◽

Idiopathic Hypercalciuria ◽

Sprague Dawley ◽

Vitamin D Receptors ◽

Low Calcium Diet ◽

Calcium Reabsorption ◽

Renal Tubular ◽

Intestinal Ca Absorption ◽

Tubular Calcium Reabsorption

The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca)-transporting organs. On a normal-Ca diet, 1,25(OH)2D3 (1,25D) increases urine (U) Ca to a greater extent in GHS than in controls [Sprague-Dawley (SD)]. The additional UCa may result from an increase in intestinal Ca absorption and/or bone resorption. To determine the source, we asked whether 1,25D would increase UCa in GHS fed a low-Ca (0.02%) diet (LCD). With 1,25D, UCa in SD increased from 1.2 ± 0.1 to 9.3 ± 0.9 mg/day and increased more in GHS from 4.7 ± 0.3 to 21.5 ± 0.9 mg/day ( P < 0.001). In GHS rats on LCD with or without 1,25D, UCa far exceeded daily Ca intake (2.6 mg/day). While the greater excess in UCa in GHS rats must be derived from bone mineral, there may also be a 1,25D-mediated decrease in renal tubular Ca reabsorption. RNA expression of the components of renal Ca transport indicated that 1,25D administration results in a suppression of klotho, an activator of the renal Ca reabsorption channel TRPV5, in both SD and GHS rats. This fall in klotho would decrease tubular reabsorption of the 1,25D-induced bone Ca release. Thus, the greater increase in UCa with 1,25D in GHS fed LCD strongly suggests that the additional UCa results from an increase in bone resorption, likely due to the increased number of VDR in the GHS rat bone cells, with a possible component of decreased renal tubular calcium reabsorption.

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Effect of phosphorus depletion on intestinal calcium and phosphorus absorption.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1979.236.4.e451 ◽

1979 ◽

Vol 236 (4) ◽

pp. E451 ◽

Cited By ~ 1

Author(s):

D B Lee ◽

N Brautbar ◽

M W Walling ◽

V Silis ◽

J W Coburn ◽

...

Keyword(s):

Male Rats ◽

Dihydroxyvitamin D3 ◽

Phosphorus Absorption ◽

32P Uptake ◽

P Balance ◽

Ad Libitum ◽

Effect Of Pd ◽

Phosphorus Depletion ◽

Intestinal Ca Absorption

Intestinal calcium (Ca) hyperabsorption is a well-documented feature of experimental phosphorus depletion (PD). To further evaluate the effect of PD on Ca absorption we studied metabolic balance and in vitro everted duodenal sac uptake of Ca and phosphorus (P) in weanling male rats. Animals were assigned to three dietary groups: normal, 0.3% P ad libitum (NP); low, 0.03% P ad libitum (LP); and normal, 0.3% P but pair-fed with assigned LP mates (NP-PF). Results indicate that although PD led to an early but unsustained increase in 45Ca uptake by the everted duodenal sac in vitro, net intestinal Ca retention is consistently decreased in rats on the LP diet compared with rats eating either the NP or NP-PF diet. The reduction in net intestinal Ca absorption is reflected by an increase in fecal Ca, both in absolute quantities and in proportion to dietary Ca intake. The initial negative P balance after the initiation of the LP diet was promptly, albeit precariously, corrected. This was associated with a sustained increase in duodenal 32P uptake in vitro and virtual cessation of growth. Because the biosynthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its accumulation in intestinal mucosa have been reported to increase with PD, our study represents an example in which the physiological interrelationship between the activity of 1,25(OH)2D3 and intestinal Ca absorption may be dissociated.

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Calcium Transporter 1 and Epithelial Calcium Channel Messenger Ribonucleic Acid Are Differentially Regulated by 1,25 Dihydroxyvitamin D3 in the Intestine and Kidney of Mice

Endocrinology ◽

10.1210/en.2003-0314 ◽

2003 ◽

Vol 144 (9) ◽

pp. 3885-3894 ◽

Cited By ~ 177

Author(s):

Yurong Song ◽

Xiaorong Peng ◽

Angela Porta ◽

Hitomi Takanaga ◽

Ji-Bin Peng ◽

...

Keyword(s):

Calcium Channel ◽

Mrna Expression ◽

Dietary Calcium ◽

Mrna Levels ◽

Dihydroxyvitamin D3 ◽

Messenger Ribonucleic Acid ◽

1,25 Dihydroxyvitamin D3 ◽

Calbindin D9k ◽

Intestinal Ca Absorption ◽

Calcium Transporter

Abstract We examined the expression of calcium transporter 1 (CaT1) and epithelial calcium channel (ECaC) mRNA in the duodenum and kidney of mice. Intestinal CaT1 mRNA level increased 30-fold at weaning, coincident with the induction of calbindin-D9k expression. In contrast, renal CaT1 and ECaC mRNA expression was equal until weaning when ECaC mRNA is induced and CaT1 mRNA levels fall 70%. Long- and short-term adaptation to changes in dietary calcium (Ca) level and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] injection strongly regulated duodenal calbindin D9k and CaT1 mRNA. Following a single dose of 1,25(OH)2D3, induction of CaT1 mRNA occurred rapidly (within 3 h, peak at 6 h of 9.6 ± 0.8-fold) and preceded the induction of intestinal Ca absorption (significantly increased at 6 h, peak at 9 h). Neither renal CaT1 nor ECaC mRNA were strongly regulated by dietary calcium level or 1,25(OH)2D3 injection. Our data indicate that CaT1 and ECaC mRNA levels are differentially regulated by 1,25(OH)2D3 in kidney and intestine and that there may be a specialized role for CaT1 in kidney in fetal and neonatal development. The rapid induction of intestinal CaT1 mRNA expression by 1,25(OH)2D3, and the marked induction at weaning, suggest that CaT1 is critical for 1,25(OH)2D3-mediated intestinal Ca absorption.

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