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.

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.

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.

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.

Transepithelial calcium transport by rat cecum: high-efficiency absorptive site

1981 ◽  
Vol 240 (6) ◽  
pp. G424-G431 ◽  
Author(s):  
H. N. Nellans ◽  
R. S. Goldsmith
Keyword(s):  
Calcium Transport ◽  
High Efficiency ◽  
Calcium Absorption ◽  
Short Circuit ◽  
Calcium Fluxes ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
High Calcium ◽  
Rat Cecum

Transepithelial calcium transport has been investigated in rat cecum under in vitro voltage-clamp conditions. Under short-circuit conditions, the cecum behaves as a relatively tight epithelium for calcium fluxes, where mucosal-to-serosal (JCam leads to s) flux exceeds the reverse flux by at least 15-fold. JCanet is abolished in the presence of 1 mM N-ethylmaleimide, is inhibited by 40% with 1 mM ouabain, and is decreased by at least 60% when medium sodium is replaced by choline. Voltage-clamping experiments suggest that both electroneutral- and electrogenic-mediated calcium fluxes traverse the cell in the mucosal-to-serosal direction. Serosal-to-mucosal flux is purely diffusional and probably constrained to the paracellular pathway. In rats weighing less than 175 g, a low-calcium diet has no significant stimulatory effect on JCam leads to s, but a high-calcium diet markedly reduces this flux. These results suggest that the cecum possesses the highest density of calcium transport sites in the rat intestine and is ideally suited for bulk calcium absorption, which may be “down regulated” in response to an increased calcium load in growing animals.

Effect of thyroparathyroidectomy of calcium metabolism in rats: role of 1,25-dihydroxyvitamin D3.

1977 ◽  
Vol 233 (3) ◽  
pp. E160 ◽  
Author(s):  
R Rizzoli ◽  
H Fleisch ◽  
J P Bonjour
Keyword(s):  
Calcium Absorption ◽  
Urinary Calcium ◽  
Plasma Calcium ◽  
Calcium Excretion ◽  
Calcium Balance ◽  
Dihydroxyvitamin D3 ◽  
Calcium Fluxes ◽  
1,25 Dihydroxyvitamin D3 ◽  
Bone Calcium

Thyroparathyroidectomy (TPTX) decreases plasma calcium, bone formation and resorption, and tubular reabsorption of calcium. It also reduces the production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] which very likely results in the decrease in the intestinal calcium absorption (Vna) observed after TPTX. We have examined whether the influence of TPTX on plasma calcium and bone calcium fluxes could be corrected by doses of 1,25-(OH)2D3 (2 X 13 pmol/day ip), which just normalize Vna. The study was made by calcium balance and 45Ca kinetics in rats receiving a normal supply of vitamin D3. The results show that in TPTX rats physiological doses of 1,25-(OH)2D3 increased plasma calcium and decreased plasma phosphate. Calcium retention was not fully corrected because 1,25-(OH)2D3 increased urinary calcium excretion. The deposition into and the release of calcium from bone were enhanced by 1,25-(OH)2D3 but remained lower than in pair-fed sham-operated animals. Thus, in as much as the diminished renal production of 1,25-(OH)2D3 in TPTX is entirely responsible for the reduced Vna, the decrease in 1,25-(OH)2D3 could only partly explain the effect of thyroparathyroidectomy on bone calcium fluxes.

Calcium transport in turtle bladder

1987 ◽  
Vol 253 (6) ◽  
pp. R917-R921
Author(s):  
S. Sabatini ◽  
N. A. Kurtzman
Keyword(s):  
Calcium Transport ◽  
Calcium Absorption ◽  
Short Circuit ◽  
Open Circuit ◽  
Calcium Flux ◽  
Bladder Epithelium ◽  
Control Value ◽  
Sodium Calcium ◽  
Turtle Bladder ◽  
Absorptive Flux

Unidirectional 45Ca fluxes were measured in the turtle bladder under open-circuit and short-circuit conditions. In the open-circuited state net calcium flux (JnetCa) was secretory (serosa to mucosa) and was 388.3 +/- 84.5 pmol.mg-1.h-1 (n = 20, P less than 0.001). Ouabain (5 X 10(-4) M) reversed JnetCa to an absorptive flux (serosal minus mucosal flux = -195.8 +/- 41.3 pmol.mg-1.h-1; n = 20, P less than 0.001). Amiloride (1 X 10(-5) M) reduced both fluxes such that JnetCa was not significantly different from zero. Removal of mucosal sodium caused net calcium absorption; removal of serosal sodium caused calcium secretion. When bladders were short circuited, JnetCa decreased to approximately one-third of control value but remained secretory (138.4 +/- 54.3 pmol.mg-1.h-1; n = 9, P less than 0.025). When ouabain was added under short-circuit conditions, JnetCa was similar in magnitude and direction to ouabain under open-circuited conditions (i.e., absorptive). Tissue 45Ca content was approximately equal to 30-fold lower when the isotope was placed in the mucosal bath, suggesting that the apical membrane is the resistance barrier to calcium transport. The results obtained in this study are best explained by postulating a Ca2+-ATPase on the serosa of the turtle bladder epithelium and a sodium-calcium antiporter on the mucosa. In this model, the energy for calcium movement would be supplied, in large part, by the Na+-K+-ATPase. By increasing cell sodium, ouabain would decrease the activity of the mucosal sodium-calcium exchanger (or reverse it), uncovering active calcium transport across the serosa.

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