Independence of 1,25-dihydroxyvitamin D3-mediated calcium transport from de novo RNA and protein synthesis.

The biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3 was compared with 1,25-dihydroxyvitamin D3 in the rat. The 24,24-difluoro-1,25-dihydroxyvitamin D3 has a potency of approximately 5-10 times that of 1,25-dihydroxyvitamin D3 in the known in vivo vitamin D responsive systems. These systems include intestinal calcium transport, bone calcium mobilization, calcification of epiphyseal plate cartilage, and elevation of plasma calcium and phosphorus concentrations. Thus, 24,24-difluoro-1,25-dihydroxyvitamin D3 is the first known analogue with higher potency than 1,25-dihydroxyvitamin D3 in vivo.

Download Full-text

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.246.3.g268 ◽

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.

Download Full-text

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.2.g189 ◽

1984 ◽

Vol 247 (2) ◽

pp. G189-G192 ◽

Cited By ~ 3

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.

Download Full-text