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.

Effects of 1,25-dihydroxyvitamin D3 on colonic calcium transport in vitamin D-deficient and normal rats

1984 ◽  
Vol 246 (3) ◽  
pp. G268-G273
Author(s):  
M. J. Favus ◽  
C. B. Langman
Keyword(s):  
Vitamin D ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Biological Response ◽  
Vehicle Control ◽  
Normal Diet ◽  
Dihydroxyvitamin D3 ◽  
Vitamin D Intake ◽  
1,25 Dihydroxyvitamin D3

To determine whether prior vitamin D intake influences the intestinal calcium absorptive action of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], we measured in vitro the two unidirectional transepithelial fluxes of calcium across descending colon segments from rats fed either a vitamin D-deficient or normal diet and injected with either 10, 25, or 75 ng of 1,25(OH)2D3 or vehicle alone. Vitamin D deficiency abolished net calcium absorption [J net, -2 +/- 2 vs. 12 +/- 2 (SE) nmol X cm-2 X h-1, P less than 0.001], and 10 ng of 1,25(OH)2D3 raised J net to levels found in normal rats. Larger doses (25 and 75 ng) increased J net above levels in normal rats given the same dose. In normal rats only 75 ng of 1,25(OH)2D3 increased calcium J net above vehicle control values (12 +/- 2 vs. 38 +/- 4 nmol X cm-2 X h-1, P less than 0.001). Circulating 1,25(OH)2D3 measured by radioreceptor assay was well correlated with calcium transport. For each dose of 1,25(OH)2D3 higher serum 1,25(OH)2D3 levels were reached in vitamin D-deficient rats. Only the 75-ng dose increased circulating 1,25(OH)2D3 and colonic calcium transport in normal rats. Intravenous [3H]-1,25(OH)2D3 disappeared more rapidly from the circulation of normal rats, suggesting that accelerated metabolic degradative processes for 1,25(OH)2D3 may be present in normal but not in vitamin D-deficient rats and may account for the lack of a biological response to 1,25(OH)2D3 in normal animals.

Effect of 1,25-dihydroxyvitamin D3 on calcium absorption in the colon of healthy humans

1984 ◽  
Vol 247 (2) ◽  
pp. G189-G192 ◽  
Author(s):  
W. C. Grinstead ◽  
C. Y. Pak ◽  
G. J. Krejs
Keyword(s):  
Short Bowel Syndrome ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Calcium Deficiency ◽  
Entire Colon ◽  
Dihydroxyvitamin D3 ◽  
Short Bowel ◽  
1,25 Dihydroxyvitamin D3 ◽  
Healthy Humans ◽  
Perfusion Studies

Calcium absorption in patients with short bowel syndrome is significantly higher when the colon is left intact. To study calcium transport in the large bowel, we investigated whether exogenous 1,25-dihydroxyvitamin D3 [1,25(OH2)D3] can induce or enhance colonic calcium absorption in healthy subjects ingesting a normal diet. Steady-state colon perfusion studies were performed before and after 1 wk of 1,25(OH)2D3 administration (2 micrograms/day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration rose from 23.0 +/- 2.2 to 39.5 +/- 4.3 pg/ml (mean +/- SE, P less than 0.01). In the basal state the mean net movement of calcium was not significantly different from zero when a 5 mM calcium gluconate solution was perfused (100 +/- 84 mumol X h-1 X entire colon secreted-1). Vitamin D administration resulted in a significant change toward calcium absorption (106 +/- 47 mumol X h-1 X entire colon absorbed-1, P less than 0.02). 1,25(OH)2D3 had no effect on colonic magnesium, phosphate, water, and electrolyte movement. This study demonstrates that in healthy humans exogenous 1,25(OH)2D3 can change colonic calcium movement toward absorption. We suspect that similar changes in colonic calcium transport are caused by endogenous 1,25(OH)2D3 when calcium deficiency has occurred in short bowel syndrome.

Pathophysiology of hypercalciuria

1984 ◽  
Vol 247 (1) ◽  
pp. F1-F13 ◽  
Author(s):  
F. L. Coe ◽  
D. A. Bushinsky
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mineral Content ◽  
Bone Mineral ◽  
Calcium Homeostasis ◽  
Calcium Transport ◽  
Mineral Content ◽  
Renal Tubule ◽  
Urine Calcium ◽  
Dihydroxyvitamin D3 ◽  
Calcium Reabsorption

The mechanisms responsible for hypercalciuria may involve intestinal calcium transport, renal tubule calcium reabsorption, and the regulation of bone mineral content. Both parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may alter urine calcium. For these reasons, understanding the pathogenesis of hypercalciuria in patients has proven to be difficult. We present here an analysis of pathways that regulate systemic calcium homeostasis and of the various mechanisms that have been proposed to explain normocalcemic hypercalciuria in humans. Available evidence seems to implicate disordered regulation of 1,25(OH)2D3 as a basis for at least one common form of hypercalciuria.

Effects of 1,25(OH)2D3 and calcium channel blockers on cecal calcium transport in the rat

1985 ◽  
Vol 248 (6) ◽  
pp. G676-G681 ◽  
Author(s):  
M. J. Favus ◽  
E. Angeid-Backman
Keyword(s):  
Vitamin D ◽  
Calcium Channel ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Channel Blockers ◽  
Dihydroxyvitamin D3 ◽  
High Concentrations ◽  
Absorptive Flux ◽  
Mucosal Side

To determine whether calcium transport across rat cecum is vitamin D dependent, we measured in vitro bidirectional calcium fluxes under short-circuited conditions across cecum from rats that were vitamin D deficient, vitamin D replete, or vitamin D deficient or vitamin D replete and injected with either 10, 25, or 75 ng of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] daily for 4 days before study. Vitamin D deficiency decreased net calcium absorption (Jnet) by reducing the mucosal-to-serosal absorptive flux (Jm----s) from 168 +/- 18 to 33 +/- 5 nmol X cm-2 X h-1 (mean +/- SE, P less than 0.0001). Twenty-five nanograms of 1,25(OH)2D3 raised Jm----s to 124 +/- 17 nmol X cm-2 X h-1, not different from values in vitamin D-replete rats. Although active calcium absorption by cecum appears to respond to vitamin D, calcium Jm----s is near maximal under normal conditions, and further stimulation follows only pharmacological doses of 1,25(OH)2D3. The in vitro addition of the calcium channel blocker verapamil (5 X 10(-5) M) to the mucosal side of cecum from vitamin D-replete rats reduced calcium Jm----s, but lower concentrations of verapamil or nitrendipine (10(-5) to 10(-9) M) did not reduce calcium Jm----s. The lack of inhibition by low concentrations of channel blockers suggest that the plasma membrane channels for calcium translocation across intestinal epithelium may not be analogous to voltage-dependent calcium channels in excitable tissue. The inhibition of cecal calcium transport that was blocked by high concentrations of verapamil may represent a nonspecific effect of the agent.

Duodenal and ileal calcium absorption in the rat and effects of vitamin D

1983 ◽  
Vol 244 (6) ◽  
pp. G695-G700 ◽  
Author(s):  
D. Pansu ◽  
C. Bellaton ◽  
C. Roche ◽  
F. Bronner
Keyword(s):  
Vitamin D ◽  
Calcium Binding ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Cytosolic Calcium ◽  
Chemical Gradient ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Loop Procedure ◽  
Proximal Intestine

An in situ ligated loop procedure was applied to dissect transmural calcium transport in the intestine into two components, a saturable and a nonsaturable process. The existence of two such processes was confirmed in the duodenum, but ileal calcium transport was devoid of the saturable component. There was a small saturable component in the upper jejunum. The level of CaBP, the vitamin D-dependent cytosolic calcium-binding protein (Mr, approximately or equal to 9,000), corresponded to the magnitude of the saturable component. No CaBP was detected in the ileum. Vitamin D dependence of the saturable component was established by inducing it in the duodenum of vitamin D-deficient animals following intraperitoneal injection of 1,25-dihydroxyvitamin D3. In these same animals, conversely, the ileum did not respond to exogenous 1,25-dihydroxyvitamin D3. This confirms the absence in the ileum of the saturable component of transmural calcium movement and the fact that the nonsaturable component is not vitamin D dependent. Everted sac experiments also showed that duodenal sacs from vitamin D-replete or -repleted animals transported calcium against a chemical gradient, whereas ileal sacs did not. Vitamin D regulation of intestinal calcium absorption thus occurs only in the proximal intestine, even though calcium is absorbed down its chemical gradient all along the small intestine.

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.

Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat

1982 ◽  
Vol 242 (6) ◽  
pp. G575-G581 ◽  
Author(s):  
M. J. Favus ◽  
F. L. Coe ◽  
S. C. Kathpalia ◽  
A. Porat ◽  
P. K. Sen ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Idiopathic Hypercalciuria ◽  
Calcium Excretion ◽  
Dihydroxyvitamin D3 ◽  
Ussing Chambers ◽  
1,25 Dihydroxyvitamin D3 ◽  
Descending Colon

Previous studies have shown that thiazide diuretic agents reverse secondary hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium absorption rates in patients with idiopathic hypercalciuria of the renal-leak variety. We have investigated whether thiazides can reverse the secondary increase in serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but adequate in phosphorus and vitamin D. We found that LCD increased circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2- 0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15 vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut sacs from duodenum, ileum, and descending colon, and net calcium absorption by descending colon studied in Ussing chambers in vitro. Chlorothiazide (CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ, 0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3 (chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or intestinal calcium transport. The drug caused no change in serum 1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium absorption, CTZ reduced urine calcium excretion greatly but did not alter intestinal calcium absorption.

Effects of trifluoperazine, ouabain, and ethacrynic acid on intestinal calcium transport

1983 ◽  
Vol 244 (2) ◽  
pp. G111-G115 ◽  
Author(s):  
M. J. Favus ◽  
E. Angeid-Backman ◽  
M. D. Breyer ◽  
F. L. Coe
Keyword(s):  
Calcium Transport ◽  
Ethacrynic Acid ◽  
Calcium Absorption ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Transepithelial Transport ◽  
Dihydroxyvitamin D3 ◽  
Calcium Fluxes ◽  
1,25 Dihydroxyvitamin D3 ◽  
Descending Colon

Bidirectional steady-state calcium fluxes were measured in vitro under short-circuited conditions in segments of rat duodenum and descending colon. The calcium-activated ATPase (Ca-ATPase) inhibitor trifluoperazine (TFP, 0.1 mM) reduced net calcium absorption in both tissues by decreasing the absorptive flux from mucosa to serosa (Jm leads to s) without consistently altering the secretory flux from serosa to mucosa. 1,25-Dihydroxyvitamin D3 administration (50 ng/day for 4 days) increased net calcium absorption by increasing Jm leads to s, and TFP reduced Jm leads to s to the same extent across tissues from vehicle- or 1,25-dihydroxyvitamin D3-treated animals. Na-K-ATPase inhibitors ouabain and ethacrynic acid both reduced short-circuit current without affecting calcium fluxes. These data suggest that Ca-ATPase, located in the basolateral membrane of intestinal epithelial cells, plays a role in the transepithelial transport of calcium. More general effects of TFP on intestinal epithelium may also contribute to the reduction in calcium fluxes. Duodenal and descending colon calcium transport appears independent of transcellular sodium transport mediated by Na-K-ATPase.

Effect of Hydrochlorothiazide on 1,25-dihydroxyvitamin D3-induced Changes in Calcium Metabolism in Experimental Hypoparathyroidism in Rats

1981 ◽  
Vol 60 (1) ◽  
pp. 101-107 ◽  
Author(s):  
R. Rizzoli ◽  
K. Hugi ◽  
H. Fleisch ◽  
J.-P. Bonjour
Keyword(s):  
Calcium Absorption ◽  
Kinetic Studies ◽  
Chronic Administration ◽  
Plasma Calcium ◽  
Intestinal Calcium Absorption ◽  
Calcium Deposition ◽  
Calcium Excretion ◽  
Calcium Balance ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

1. Chronic administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can normalize plasma calcium in human hypoparathyroidism and in thyroparathyroidectomized animals. The effect of 1,25(OH)2D3 on plasma calcium is associated with an increase in urinary calcium excretion. In an attempt to prevent this increase, thyroparathyroidectomized rats receiving 1,25(OH)2D3 were also treated with hydrochlorothiazide for 9–11 days. 2. Calcium clearance studies show that hydrochlorothiazide stimulated the tubular reabsorption of calcium in thyroparathyroidectomized rats treated with 1,25(OH)2D3. 3. Calcium balance and kinetic studies indicated that hydrochlorothiazide decreased 1,25(OH)2D3-induced hypercalciuria in thyroparathyroidectomized rats. Hydrochlorothiazide did not affect the 1,25(OH)2D3-induced increase in plasma calcium. The hypocalciuric effect of hydrochlorothiazide was not associated with significant changes in calcium deposition into or release from bone. 4. In thyroparathyroidectomized rats treated with 1,25(OH)2D3 the hypocalciuric effect of hydrochlorothiazide was associated with a fall in intestinal calcium absorption. Overall, the calcium balance was unaffected. 5. Thus it appears that hydrochlorothiazide reduces the 1,25(OH)2D3-induced hypercalciuria in parathyroid hormone-deficient animals by decreasing intestinal calcium absorption. Despite the decreased absorption, hydrochlorothiazide does not reduce the 1,25(OH)2D3-induced increase in plasma calcium.

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