Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats

2012 ◽  
Vol 302 (7) ◽  
pp. E852-E863 ◽  
Author(s):  
Prapaporn Jongwattanapisan ◽  
Panan Suntornsaratoon ◽  
Kannikar Wongdee ◽  
Nitita Dorkkam ◽  
Nateetip Krishnamra ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Calcium Transport ◽  
Calcium Metabolism ◽  
Calcium Absorption ◽  
Calcium Excretion ◽  
Compensatory Mechanism ◽  
Calcium Balance ◽  
Balance Study ◽  
Colonic Epithelial Cells ◽  
Calbindin D

An earlier study reported that cecal calcium absorption contributes less than 10% of total calcium absorbed by the intestine, although the cecum has the highest calcium transport rate compared with other intestinal segments. Thus, the physiological significance of the cecum pertaining to body calcium metabolism remains elusive. Herein, a 4-wk calcium balance study in cecectomized rats revealed an increase in fecal calcium loss with marked decreases in fractional calcium absorption and urinary calcium excretion only in the early days post-operation, suggesting the presence of a compensatory mechanism to minimize intestinal calcium wasting. Further investigation in cecectomized rats showed that active calcium transport was enhanced in the proximal colon but not in the small intestine, whereas passive calcium transport along the whole intestine was unaltered. Since apical exposure to calcium-sensing receptor (CaSR) agonists similarly increased proximal colonic calcium transport, activation of apical CaSR in colonic epithelial cells could have been involved in this hyperabsorption. Calcium transporter genes, i.e., TRPV6 and calbindin-D9k, were also upregulated in proximal colonic epithelial cells. Surprisingly, elevated serum parathyroid hormone levels and hyperphosphatemia were evident in cecectomized rats despite normal plasma calcium levels, suggesting that colonic compensation alone might be insufficient to maintain normocalcemia. Thus, massive bone loss occurred in both cortical and trabecular sites, including lumbar vertebrae, femora, and tibiae. The presence of compensatory colonic calcium hyperabsorption with pervasive osteopenia in cecectomized rats therefore corroborates that the cecum is extremely crucial for body calcium homeostasis.

The study of a physiological significance of prolactin in the regulation of calcium metabolism during pregnancy and lactation in rats

1998 ◽  
Vol 76 (2) ◽  
pp. 218-228 ◽  
Author(s):  
Sutada Lotinun ◽  
Liangchai Limlomwongse ◽  
Nateetip Krishnamra
Keyword(s):  
Body Weight ◽  
Calcium Metabolism ◽  
Turnover Rate ◽  
Calcium Absorption ◽  
Prolactin Secretion ◽  
Calcium Excretion ◽  
Calcium Balance ◽  
Total Calcium ◽  
Bone Calcium ◽  
Pregnancy And Lactation

Since a pharmacological dose of prolactin has previously been reported to enhance calcium absorption and bone calcium turnover, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in the balance studies of Wistar rats between days 17 and 20 of first (P1) and fourth (P4) pregnancy and between days 12 and 15 of lactation (L). Each group was divided into 3 subgroups: one subgroup was given 0.9% NaCl (control); one was given 0.3 mg bromocriptine/100 g body weight ip twice daily for 3 days (to suppress prolactin secretion); and one was given bromocriptine and 0.25 mg prolactin/100 g body weight sc daily for 3 days. All three groups received 1 mL/100 g body weight of 1.25 mM calcium gluconate containing 2 mCi (1 Ci = 37 GBq) 45Ca daily for 3 days. Compared with the two pregnant controls, the L group had higher food consumption and higher fecal calcium excretion and lower urinary calcium excretion (% intake). Bromocriptine administration increased total calcium excretion from 59% intake to 84 and 66% intake in P1 and P4, respectively, suggesting that endogenous prolactin decreased total calcium excretion. On the other hand, exogenous prolactin had no effect on the calcium balance of P1 but increased the total calcium excretion in P4 from 57 to 66% intake. In contrast, the calcium balance of lactating rats was not altered by suppression of endogenous prolactin secretion or exogenous prolactin. Considering bone 45Ca content as representing bone Ca turnover, a lower value of bone 45Ca content indicated an accelerated bone Ca turnover. It was found that bromocriptine had no effect in P1 but decreased bone Ca turnover rate in the P4 and L groups, indicating an accelerating effect of endogenous prolactin on bone Ca turnover in the P4 and L groups. Exogenous prolactin, on the other hand, decreased bone Ca turnover rate in every group. Muscle Ca turnover was affected by bromocriptine and exogenous prolactin in the same manner as bone 45Ca contents. Interestingly, the biphasic action of prolactin was demonstrated in both calcium absorption and bone calcium turnover. It could be concluded that during pregnancy and lactation, endogenous prolactin increases food consumption, fractional calcium absorption, and bone calcium turnover, apparently to increase calcium availability for fetal development and milk calcium secretion.Key words: bone turnover, bromocriptine, calcium absorption, calcium excretion, calcium retention, prolactin.

Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human

2003 ◽  
Vol 284 (4) ◽  
pp. F628-F643 ◽  
Author(s):  
Johannes Loffing ◽  
Brigitte Kaissling
Keyword(s):  
Sodium Transport ◽  
Calcium Transport ◽  
Transport Proteins ◽  
Sodium Balance ◽  
Apical Plasma Membrane ◽  
Calcium Excretion ◽  
Fluid Composition ◽  
Calcium Balance ◽  
Distal Nephron ◽  
Transport Pathways

The final adjustment of renal sodium and calcium excretion is achieved by the distal nephron, in which transepithelial ion transport is under control of various hormones, tubular fluid composition, and flow rate. Acquired or inherited diseases leading to deranged renal sodium and calcium balance have been linked to dysfunction of the distal nephron. Diuretic drugs elicit their effects on sodium balance by specifically inhibiting sodium transport proteins in the apical plasma membrane of distal nephron segments. The identification of the major apical sodium transport proteins allows study of their precise distribution pattern along the distal nephron and helps address their cellular and molecular regulation under various physiological and pathophysiological settings. This review focuses on the topological arrangement of sodium and calcium transport proteins along the cortical distal nephron and on some aspects of their functional regulation. The availability of data on the distribution of transporters in various species points to the strengths, as well as to the limitations, of animal models for the extrapolation to humans.

Calcium metabolism in dairy sheep

1984 ◽  
Vol 102 (3) ◽  
pp. 601-608 ◽  
Author(s):  
S. Economides
Keyword(s):  
Calcium Intake ◽  
Calcium Metabolism ◽  
Dry Matter ◽  
Calcium Absorption ◽  
Urinary Calcium ◽  
Calcium Balance ◽  
Dairy Sheep ◽  
Deficient Diet ◽  
Pregnant Sheep ◽  
Calcium Loss

SummaryCalcium metabolism in dairy sheep was studied using radioisotope and balance techniques. The rate of calcium absorption increased, but the efficiency of calcium absorption decreased, with increasing calcium intake in dry sheep. Endogenous faecal and urinary calcium losses, and the rate of calcium absorption, decreased, but the efficiency of calcium absorption increased in pregnant sheep given a calcium-deficient diet. The rate and the efficiency of calcium absorption and the calcium balance of lactating ewes were not influenced by the prepartum level of calcium intake, when calcium intake in early lactation was high. Endogenous faecal calcium loss was related to dry-matter intake, and total faecal calcium loss was related to calcium intake.

Calcium transport in renal epithelial cells

1993 ◽  
Vol 264 (2) ◽  
pp. F181-F198 ◽  
Author(s):  
P. A. Friedman ◽  
F. A. Gesek
Keyword(s):  
Calcium Transport ◽  
Calcium Absorption ◽  
Cellular Level ◽  
Extracellular Calcium ◽  
Calcium Excretion ◽  
Dihydroxyvitamin D3 ◽  
Calcium Reabsorption ◽  
Distal Tubules ◽  
Calcium Resorption ◽  
Editorial Review

Extracellular calcium homeostasis involves coordinated calcium absorption by the intestine, calcium resorption from bone, and calcium reabsorption by the kidney. This review addresses the mechanism and regulation of renal calcium transport. Calcium reabsorption occurs throughout the nephron. However, distal tubules are the nephron site at which calcium reabsorption is regulated by parathyroid hormone, calcitonin, and 1 alpha,25-dihydroxyvitamin D3 and where the magnitude of net reabsorption is largely determined. These and related observations underscore the view that distal tubules are highly specialized to permit fine regulation of calcium excretion in response to alterations in extracellular calcium levels. Progress in understanding the mechanism and regulation of calcium transport has emerged from application of single cell fluorescence, patch clamp, and molecular biological approaches. These techniques permit the examination of ion transport at the cellular level and its regulation at subcellular and molecular levels. This editorial review focuses on recent and emerging observations and attempts to integrate them into models of cellular calcium transport.

Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption

1986 ◽  
Vol 251 (1) ◽  
pp. F17-F24 ◽  
Author(s):  
D. A. Bushinsky ◽  
M. J. Favus ◽  
C. B. Langman ◽  
F. L. Coe
Keyword(s):  
Calcium Absorption ◽  
Chronic Administration ◽  
Urinary Calcium ◽  
Intestinal Calcium Absorption ◽  
Calcium Excretion ◽  
Calcium Balance ◽  
Urine Calcium ◽  
Calcium Diet ◽  
Filtered Load ◽  
Urine Calcium Excretion

Furosemide produces chronic hypercalciuria. The source of the additional urinary calcium is not known but must be either bone mineral or calcium absorbed by the intestine. Without bone calcium dissolution or increased absorption the filtered load of calcium would fall and urinary calcium excretion would return to pretreatment levels. To determine whether furosemide alters intestinal calcium absorption, we fed furosemide (75 mg . kg body-1 wt . day-1) to 11 rats eating 15 g/day of a 0.60% calcium diet. Compared with 11 control rats, furosemide increased urine calcium (15.6 +/- 0.8 mg/5 days vs. 4.1 +/- 0.3, P less than 0.001). Fecal calcium excretion fell (194 +/- 7 mg/5 days vs. 223 +/- 12, P less than 0.05), indicating an increase in intestinal calcium absorption sufficient to sustain the hypercalciuria. The increase in absorption occurred without an increase in the level of serum 1,25-dihydroxycholecalciferol (180 +/- 20 pg/ml vs. 220 +/- 16, furosemide vs. control, respectively, P = NS). To determine whether the intestinal effect of furosemide persists after the initial sodium diuresis abates, we analyzed only the last 3 days of balance. Again, rats fed furosemide had increased urine excretion and intestinal absorption of calcium, so that net calcium balance was not different from that of controls. Twelve additional rats were fed a 0.02% calcium diet to which 35 mg . kg body wt-1 . day-1 of furosemide was added. Compared with eleven controls, urine calcium increased and fecal calcium excretion again fell, but balance was not different. Chronic administration of furosemide increases intestinal calcium absorption enough to permit urine calcium excretion to remain elevated without the necessity for bone dissolution.

scholarly journals Vitamin D Receptor Binding with DNA in Duodenal Crypt, Duodenal Villi, and Colonic Epithelial Cells of Mice

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Dennis A. Aldea ◽  
Rohit Aita ◽  
Sohaib Hassan ◽  
Evan S. Cohen ◽  
Joseph Hur ◽  
...  
Keyword(s):  
Vitamin D ◽  
Transcription Factor ◽  
Dna Binding ◽  
Epithelial Cells ◽  
Vitamin D Receptor ◽  
Calcium Absorption ◽  
Intestinal Epithelial Cells ◽  
Calcium Deficiency ◽  
Intestinal Epithelial ◽  
Colonic Epithelial Cells

Vitamin D receptor (VDR) is a transcription factor that mediates calcium absorption by intestinal epithelial cells. Although calcium absorption is ca-nonically thought to occur only in the small intestine, recent studies have shown that VDR activity in the co-lon alone is sufficient to prevent calcium deficiency in mice. Here, we further investigate VDR activity in the colon. We assess VDR-DNA binding in mouse duodenal crypt, duodenal villi, and colonic epithelial cells using Chromatin Immunoprecipitation se-quencing (ChIP-seq). We find that most VDR-respon-sive elements are common to all intestinal epithelial cells, though some VDR-responsive elements are re-gionally-enriched and exhibit greater VDR-binding affinity in either duodenal epithelial cells or colonic epithelial cells. We also assess chromatin accessibil-ity in the same three cell types using Assay for Trans-posase-Accessible Chromatin sequencing (ATAC-seq). By integrating the VDR ChIP-seq and ATAC-seq data, we find that regionally-enriched VDR-re-sponsive elements exhibit greater chromatin acces-sibility in the region of their enrichment. Finally, we assess the transcription factor motifs present in VDR-responsive elements. We find that duodenum- and colon-enriched VDR-responsive elements exhibit different sets of transcription factor motifs other than VDR, suggesting that VDR may act together with dif-ferent partner transcription factors in the two re-gions. Our work is the first investigation of VDR-DNA binding in the colon and provides a basis for further investigations of VDR activity in the colon.

Endurance swimming stimulates transepithelial calcium transport and alters the expression of genes related to calcium absorption in the intestine of rats

2009 ◽  
Vol 296 (4) ◽  
pp. E775-E786 ◽  
Author(s):  
Jarinthorn Teerapornpuntakit ◽  
Nitita Dorkkam ◽  
Kannikar Wongdee ◽  
Nateetip Krishnamra ◽  
Narattaphol Charoenphandhu
Keyword(s):  
Calcium Transport ◽  
Calcium Absorption ◽  
Relevant Information ◽  
Proximal Colon ◽  
Intestinal Calcium Absorption ◽  
Proximal Jejunum ◽  
Microarray Study ◽  
Expression Of Genes ◽  
Impact Exercise ◽  
Calbindin D

Endurance impact exercise, e.g., running, is known to enhance the intestinal calcium absorption. However, nonimpact exercise, e.g., swimming, is more appropriate for osteoporotic patients with cardiovascular diseases or disorders of bone and joint, but the effect of swimming on the intestinal calcium transport was unknown. This study, therefore, aimed to investigate the transepithelial calcium transport and the expression of related genes in the intestine of rats trained to swim nonstop 1 h/day, 5 days/wk for 2 wk. We found that endurance swimming stimulated calcium transport in the duodenum, proximal jejunum, and cecum, while decreasing that in the proximal colon. Swimming affected neither the transepithelial potential difference nor resistance. As demonstrated by real-time PCR, the small intestine, especially the duodenum, responded to swimming by upregulating a number of genes related to the transcellular calcium transport, i.e., TRPV5, TRPV6, calbindin-D9k, PMCA1b, and NCX1, and the paracellular calcium transport, i.e., ZO-1, ZO-2, ZO-3, cingulin, occludin, and claudins, as well as nuclear receptor of 1,25(OH)2D3. In contrast, swimming downregulated those genes in the colon. Microarray analysis showed that swimming also altered the expression of duodenal genes related to the transport of several ions and nutrients, e.g., Na+, K+, Cl−, glucose, and amino acids. In conclusion, endurance swimming enhanced intestinal calcium absorption, in part, by upregulating the calcium transporter genes. The present microarray study also provided relevant information for further investigations into the intestinal nutrient and electrolyte transport during nonimpact exercise.

Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D3-enhanced duodenal calcium transport in male mice

2012 ◽  
Vol 302 (8) ◽  
pp. E903-E913 ◽  
Author(s):  
Pissared Khuituan ◽  
Jarinthorn Teerapornpuntakit ◽  
Kannikar Wongdee ◽  
Panan Suntornsaratoon ◽  
Nipaporn Konthapakdee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Fibroblast Growth Factor ◽  
Calcium Absorption ◽  
Ussing Chamber ◽  
Intestinal Calcium Absorption ◽  
Fibroblast Growth ◽  
Male Mice ◽  
Calbindin D ◽  
Fgf 23

Despite being widely recognized as the important bone-derived phosphaturic hormone, whether fibroblast growth factor (FGF)-23 modulated intestinal calcium absorption remained elusive. Since FGF-23 could reduce the circulating level of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], FGF-23 probably compromised the 1,25(OH)2D3-induced intestinal calcium absorption. FGF-23 may also exert an inhibitory action directly through FGF receptors (FGFR) in the intestinal cells. Herein, we demonstrated by Ussing chamber technique that male mice administered 1 μg/kg 1,25(OH)2D3 sc daily for 3 days exhibited increased duodenal calcium absorption, which was abolished by concurrent intravenous injection of recombinant mouse FGF-23. This FGF-23 administration had no effect on the background epithelial electrical properties, i.e., short-circuit current, transepithelial potential difference, and resistance. Immunohistochemical evidence of protein expressions of FGFR isoforms 1–4 in mouse duodenal epithelial cells suggested a possible direct effect of FGF-23 on the intestine. This was supported by the findings that FGF-23 directly added to the serosal compartment of the Ussing chamber and completely abolished the 1,25(OH)2D3-induced calcium absorption in the duodenal tissues taken from the 1,25(OH)2D3-treated mice. However, direct FGF-23 exposure did not decrease the duodenal calcium absorption without 1,25(OH)2D3 preinjection. The observed FGF-23 action was mediated by MAPK/ERK, p38 MAPK, and PKC. Quantitative real-time PCR further showed that FGF-23 diminished the 1,25(OH)2D3-induced upregulation of TRPV5, TRPV6, and calbindin-D9k, but not PMCA1b expression in the duodenal epithelial cells. In conclusion, besides being a phosphatonin, FGF-23 was shown to be a novel calcium-regulating hormone that acted directly on the mouse intestine, thereby compromising the 1,25(OH)2D3-induced calcium absorption.

Enhancement of calcium transport in Caco-2 monolayer through PKCζ-dependent Cav1.3-mediated transcellular and rectifying paracellular pathways by prolactin

2009 ◽  
Vol 296 (6) ◽  
pp. C1373-C1382 ◽  
Author(s):  
Narongrit Thongon ◽  
La-iad Nakkrasae ◽  
Jirawan Thongbunchoo ◽  
Nateetip Krishnamra ◽  
Narattaphol Charoenphandhu
Keyword(s):  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Protein Biosynthesis ◽  
Ussing Chamber ◽  
Calcium Flux ◽  
Channel Blockers ◽  
Voltage Dependent ◽  
Calbindin D

Previous investigations suggested that prolactin (PRL) stimulated the intestinal calcium absorption through phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), and RhoA-associated coiled-coil forming kinase (ROCK) signaling pathways. However, little was known regarding its detailed mechanisms for the stimulation of transcellular and voltage-dependent paracellular calcium transport. By using Ussing chamber technique, we found that the PRL-induced increase in the transcellular calcium flux and decrease in transepithelial resistance of intestinal-like Caco-2 monolayer were not abolished by inhibitors of gene transcription and protein biosynthesis. The PRL-stimulated transcellular calcium transport was completely inhibited by the L-type calcium channel blockers (nifedipine and verapamil) and plasma membrane Ca2+-ATPase (PMCA) inhibitor (trifluoperazine) as well as small interfering RNA targeting voltage-dependent L-type calcium channel Cav1.3, but not TRPV6 or calbindin-D9k. As demonstrated by 45Ca uptake study, PI3K and PKC, but not ROCK, were essential for the PRL-enhanced apical calcium entry. In addition, PRL was unable to enhance the transcellular calcium transport after PKCζ knockdown or exposure to inhibitors of PKCζ, but not of PKCα, PKCβ, PKCε, PKCμ, or protein kinase A. Voltage-clamping experiments further showed that PRL markedly stimulated the voltage-dependent calcium transport and removed the paracellular rectification. Such PRL effects on paracellular transport were completely abolished by inhibitors of PI3K (LY-294002) and ROCK (Y-27632). It could be concluded that the PRL-stimulated transcellular calcium transport in Caco-2 monolayer was mediated by Cav1.3 and PMCA, presumably through PI3K and PKCζ pathways, while the enhanced voltage-dependent calcium transport occurred through PI3K and ROCK pathways.

Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes

1999 ◽  
Vol 277 (1) ◽  
pp. R1-R10 ◽  
Author(s):  
Scott M. Smith ◽  
Meryl E. Wastney ◽  
Boris V. Morukov ◽  
Irina M. Larina ◽  
Laurence E. Nyquist ◽  
...  
Keyword(s):  
Calcium Metabolism ◽  
Time Course ◽  
Calcium Absorption ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Bone Specific Alkaline Phosphatase ◽  
Long Duration ◽  
Bone Calcium ◽  
Male Subjects ◽  
Markers Of Bone Formation

The loss of bone during spaceflight is considered a physiological obstacle for the exploration of other planets. This report of calcium metabolism before, during, and after long-duration spaceflight extends results from Skylab missions in the 1970s. Biochemical and endocrine indexes of calcium and bone metabolism were measured together with calcium absorption, excretion, and bone turnover using stable isotopes. Studies were conducted before, during, and after flight in three male subjects. Subjects varied in physical activity, yet all lost weight during flight. During flight, calcium intake and absorption decreased up to 50%, urinary calcium excretion increased up to 50%, and bone resorption (determined by kinetics or bone markers) increased by over 50%. Osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, increased after flight. Subjects lost ∼250 mg bone calcium per day during flight and regained bone calcium at a slower rate of ∼100 mg/day for up to 3 mo after landing. Further studies are required to determine the time course of changes in calcium homeostasis during flight to develop and assess countermeasures against flight-induced bone loss.

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