Metabolism in Vitro of 25-Hydroxycholecalciferol in Chicks Fed on Phosphorus-Deficient Diets

1978 ◽  
Vol 54 (2) ◽  
pp. 197-200 ◽  
Author(s):  
R. Swaminathan ◽  
Barbara A. Sommerville ◽  
A. D. Care
Keyword(s):  
Calcium Absorption ◽  
Plasma Calcium ◽  
Hydroxylase Activity ◽  
High Phosphorus ◽  
Phosphorus Deprivation ◽  
Low Phosphorus ◽  
Loop Technique ◽  
25 Hydroxycholecalciferol

1. Three groups of 10-days-old chicks were fed on one of three diets having phosphorus contents of 0·08 mol/kg, 0·14 mol/kg or 0·21 mol/kg. Ten days later duodenal calcium absorption by the ligated loop technique in vivo, and plasma calcium and phosphorus concentrations, were measured. In addition the metabolism in vitro of 25-hydroxycholecalciferol [25-(OH)D3] by kidney homogenates was studied. 2. In the low phosphorus group (0·08 mol/kg) calcium absorption and the activity of 25-(OH)D3-1-hydroxylase were significantly higher than those of the high phosphorus group (0·21 mol/kg). However, in the medium phosphorus group (0·14 mol/kg), calcium absorption was significantly higher although the activity of 25-(OH)D3-1-hydroxylase was not significantly higher when compared with the high phosphorus group (0·21 mol/kg). 3. It is concluded that in phosphorus deprivation, unlike in calcium deprivation, a diet very low in phosphorus is required to stimulate the renal 25-(OH)D3-1-hydroxylase activity.

Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.

1977 ◽  
Vol 232 (3) ◽  
pp. E298
Author(s):  
U Trechsel ◽  
R Schenk ◽  
J P Bonjour ◽  
R G Russell ◽  
H Fleisch
Keyword(s):  
Calcium Absorption ◽  
Bone Mineralization ◽  
Close Correlation ◽  
Plasma Calcium ◽  
Intestinal Calcium Absorption ◽  
Phosphate Salts ◽  
Dose Response Study ◽  
Skeletal Mineralization

Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.

Effect of vitamin D3 on duodenal calcium absorption in vivo during early development

1984 ◽  
Vol 246 (5) ◽  
pp. G528-G534 ◽  
Author(s):  
L. A. Dostal ◽  
S. U. Toverud
Keyword(s):  
Vitamin D ◽  
Calcium Absorption ◽  
Plasma Calcium ◽  
High Dose ◽  
Vitamin D Status ◽  
Dihydroxyvitamin D3 ◽  
Loop Technique ◽  
Plasma Calcium Level

The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D deficiency on duodenal calcium absorption in suckling and weaned rats was determined by an in situ loop technique. In vitamin D-replete (+D) rats, the linear, or nonsaturable, component of calcium absorption was very efficient in 14-day-old pups and decreased with age until 35 days. The saturable component, which was undetectable in 14-day-old pups, became detectable by 18 days of age and increased until 26 days of age. Calcium absorption was not reduced in vitamin D-deficient (-D) 14-day-old pups as compared with +D pups. A high dose of 1,25(OH)2D3 increased the plasma calcium level of +D suckling rats but had no effect on calcium absorption even with milk present in the loop. Weaned -D rats had a reduced saturable component of absorption (P less than 0.01) compared with +D rats. A high dose of 1,25(OH)2D3 significantly increased calcium absorption and plasma calcium levels of -D rats. Our results indicate that during suckling calcium absorption occurs by a process that is insensitive to vitamin D. After weaning both saturable and nonsaturable processes appear to contribute to calcium absorption, and the saturable component can be influenced by vitamin D status or a high dose of 1,25(OH)2D3.

THE ROLE OF THE PARATHYROID GLANDS IN THE ABSORPTION OF CALCIUM FROM THE SMALL INTESTINE

1970 ◽  
Vol 47 (1) ◽  
pp. 65-72 ◽  
Author(s):  
M. WINTER ◽  
E. MORAVA ◽  
G. SIMON ◽  
J. SÓS
Keyword(s):  
Small Intestine ◽  
Calcium Absorption ◽  
Normal Diet ◽  
Calcium Excretion ◽  
Deficient Diet ◽  
High Calcium ◽  
Low Phosphorus ◽  
Loop Technique

SUMMARY The absorption of calcium from duodenal and jejunal segments of the small intestine was studied in rats using an in-vivo loop technique. Previous parathyroidectomy decreased calcium absorption from both segments in rats fed a normal diet. Reduced calcium transport was greater in rats fed a calcium-deficient diet after parathyroidectomy. The slower clearance of radioactive calcium from the lumen of the intestine was not due to increased endogenous calcium excretion. Thyroidectomy, either alone or combined with parathyroidectomy, decreased calcium absorption but the effect of thyroidectomy alone requires further study. The decrease in calcium absorption after removal of the parathyroids was minimal or absent when the animals were fed a high calcium, low phosphorus, vitamin D-deficient diet or fasted 48 hr. before the experiment.

The Filter Loop Technique as a Method of Measuring Platelet Aggregation in the Flowing Blood of the Rat; the Inhibitory Activity of 5-oxo-l-cyclopentene-l-heptanoic Acid (AY-16,804) on Platelet Aggregation

1973 ◽  
Vol 30 (01) ◽  
pp. 138-147 ◽  
Author(s):  
Christopher R. Muirhead
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Suitable Model ◽  
Heptanoic Acid ◽  
Simple Method ◽  
Loop Technique ◽  
Flowing Blood ◽  
Filter Loop

SummaryThe filter loop technique which measures platelet aggregation in vivo in the flowing-blood of the rat was compared to the optical density technique of Born which is carried out in vitro with platelet rich plasma. Using these two experimental models the effect on platelet aggregation of three known inhibitors sulfinpyrazone, dipyridamole and prostaglandin E1, and a novel compound 5-oxo-l-cyclopentene-l-heptanoic acid (AY-16, 804) was determined.The effects on platelet aggregation of the known inhibitors were consistent with information in the literature. Prostaglandin E1 was the most potent inhibitor in both techniques; sulfinpyrazone inhibited aggregation in both models but was less potent than prostaglandin E1. AY-16, 804 exhibited activity in vitro and in vivo similar to that of sulfinpyrazone. Dipyridamole did not inhibit platelet aggregation in vivo and did not inhibit aggregation in vitro in concentrations at which it remained soluble.The filter loop technique is a suitable model for measuring platelet aggregation in the flowing blood of the rat. It is a relatively simple method of determining aggregation and easily adapted to other species.

Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation

1984 ◽  
Vol 246 (2) ◽  
pp. E168-E173 ◽  
Author(s):  
Y. Tanaka ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Inorganic Phosphorus ◽  
Hydroxylase Activity ◽  
Deficient Diet ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Dietary Phosphorus ◽  
Low Calcium

The effects of thyroparathyroidectomy, parathyroid hormone, 1,25-dihydroxyvitamin D3, dietary calcium, dietary phosphorus, age, and sex on the renal 25-hydroxyvitamin D3 1- and 24-hydroxylases measured in vitro in rats have been studied. Thyroparathyroidectomy of vitamin D-deficient rats abolishes 25-hydroxyvitamin D3 1-hydroxylase activity, and administration of bovine parathyroid extract to the thyroparathyroidectomized rat restores diminished 1-hydroxylase activity. Both suppression and restoration of the enzyme activities require many hours (18-24 h) independent of rapid changes in serum calcium and inorganic phosphorus levels in response to these manipulations. Administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats suppresses 25-hydroxyvitamin D3 1-hydroxylase activity and stimulates 25-hydroxyvitamin D3 24-hydroxylase activity within 48 h. Rats maintained on a low-calcium or a low-phosphorus diet with a daily supplement of 20 IU vitamin D3 show high 25-hydroxyvitamin D3 1-hydroxylase activity and low 24-hydroxylase activity as compared with rats similarly treated but fed a diet containing adequate calcium or adequate phosphorus. When vitamin D-sufficient rats having suppressed renal 25-hydroxyvitamin D3 1-hydroxylase activity are placed on a low-calcium vitamin D-deficient diet for 7 days, the 1-hydroxylase activity is greatly stimulated in 6-wk-old rats but much less so in rats with advancing age.

Calcium absorption and intestinal calcium-binding protein: quantitative relationship.

1979 ◽  
Vol 236 (5) ◽  
pp. E556 ◽  
Author(s):  
J J Feher ◽  
R H Wasserman
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Calcium Binding ◽  
Calcium Absorption ◽  
Binding Protein ◽  
Quantitative Relationship ◽  
Calcium Binding Protein ◽  
Vitamin D Status ◽  
Loop Technique

The concentration of the vitamin D-induced calcium-binding protein (CaBP) and calcium absorption from the duodenum were investigated in chicks with an in vivo ligated-loop technique. The relation between CaBP and calcium absorption was dependent on a) source of vitamin D activity (either vitamin D3 or 1,25-dihydroxycholecalciferol); b) dosage of vitamin D3; c) time after administration of vitamin D3 to rachitic animals. To aid in the interpretation of these results, a phenomenological model was developed in which CaBP was viewed as being linearly related to a portion of calcium absorption. The model, when applied to the data, suggests that there is a "nonfunctional" pool of CaBP the size of which is determined by the vitamin D status of the animal. After correction for this nonfunctional pool, the proportionality between CaBP and calcium absorption is independent of the vitamin D status of the animal.

scholarly journals Metabolism of phenylalanine in mice homozygous for the gene ‘dilute lethal’

1970 ◽  
Vol 119 (5) ◽  
pp. 895-903 ◽  
Author(s):  
L. I. Woolf ◽  
A. Jakubovic ◽  
F. Woolf ◽  
P. Bory
Keyword(s):  
Natural History ◽  
Phenylalanine Hydroxylase ◽  
Disease Process ◽  
Particulate Fraction ◽  
Hydroxylase Activity ◽  
Phenylpyruvic Acid ◽  
History Of

Mice homozygous for dl have been suggested as models for phenylketonuria. We found: (1) the concentration of phenylalanine in the blood was normal at all ages examined; (2) phenylalanine hydroxylase activity in the liver in vitro equalled that in unaffected littermates; (3) the apparent Km values for phenylalanine and cofactor respectively in dl/dl mice were the same as in their normal littermates; (4) inhibition of the overall reaction by the particulate fraction, excess of substrate, excess of cofactor or phenylpyruvic acid showed no difference between dl/dl mice and their unaffected littermates; (5) phenylalanine injected in vivo had equal, small, effects on phenylalanine hydroxylase activity of the liver measured in vitro in the two groups of mice. An explanation of the findings of other workers, based on the natural history of the disease process, is tentatively put forward.

Effect of hypophysectomy on calcium transport by rat duodenum.

1977 ◽  
Vol 232 (2) ◽  
pp. E229
Author(s):  
E L Krawitt ◽  
A S Kunin ◽  
H W Sampson ◽  
B F Bacon
Keyword(s):  
Calcium Transport ◽  
Calcium Absorption ◽  
Plasma Flux ◽  
Perfusion Technique ◽  
Intestinal Length ◽  
Absorption Studies ◽  
Luminal Perfusion ◽  
Rat Duodenum

To examine the effect of hypophysectomy on intestinal calcium absorption, studies were performed on immature rats 7, 14, and 21 days after hypophysectomy. Duodenal calcium transport was measured in vitro utilizing everted gut sacs and in vivo by a luminal perfusion technique. Hypophysectomy produced no differences in the ability of everted gut sacs to transport calcium. Similarly, when in vivo transport data were expressed on the basis of intestinal length, no significant differences were noted. However, when transport data were expressed on the basis of mucosal weight, increases in absorption and lumen-to-plasma fluxes were apparent in hypophysectomized animals. No differences were seen in plasma-to-lumen fluxes. The results indicate that when the transport data are corrected for mass of intestinal mucosa, the duodenum from hypophysectomized animals absorbs calcium more avidly due to an increase in lumen-to-plasma flux.

Development of a novel 1,25(OH)2-vitamin D3 analog with potent ability to induce HL-60 cell differentiation without modulating calcium metabolism

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 75-82 ◽  
Author(s):  
JY Zhou ◽  
AW Norman ◽  
M Akashi ◽  
DL Chen ◽  
MR Uskokovic ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Calcium Metabolism ◽  
Calcium Absorption ◽  
Leukemic Cells ◽  
Inhibition Of Proliferation ◽  
Myc Oncogene ◽  
Differentiation And Proliferation ◽  
Bone Abnormalities

We describe several novel analogs of the seco-steroid 1,25(OH)2-vitamin D3[1,25(OH)2D3] and their effects on differentiation and proliferation of HL-60 human myeloid leukemic cells in vitro as well as their effects on calcium metabolism in vivo. The 1 alpha-25(OH)2–16ene-23yne-26,27F6- vitamin D3 is the most potent analog reported to date, having about 80- fold more activity than the reference 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of HL-60 cells. Also, this analog decreased RNA expression of MYC oncogene in HL-60 by 90% at 5 x 10(-10) mol/L. Intriguingly, intestinal calcium absorption and bone calcium mobilization mediated in vivo by 1 alpha-25(OH)2–16ene-23yne- 26,27F6-D3 was found to be markedly (15-fold) less than that of 1,25(OH)2D3. In addition, 1 alpha-25(OH)2D3 bound to 1,25(OH)2D3 receptors of both HL-60 and intestine more avidly than did 1 alpha- 25(OH)2–16ene-23yne-26,27F6-D3. This novel analog may open up new therapeutic strategies for several hematopoietic, skin, and bone abnormalities and may provide a new tool to understand how vitamin D3 seco-steroids induce cellular differentiation.

NEW SYNTHETIC STEROIDS WHICH INHIBIT RAT GONADAL STEROIDOGENIC ENZYMES BOTH IN VITRO AND IN VIVO

1973 ◽  
Vol 73 (1) ◽  
pp. 146-170 ◽  
Author(s):  
Allen S. Goldman ◽  
Jan-Åke Gustafsson ◽  
Sven A. Gustafsson
Keyword(s):  
Female Rats ◽  
Gas Liquid Chromatography ◽  
Liquid Chromatography Mass Spectrometry ◽  
Hydroxylase Activity ◽  
Hormone Production ◽  
Oxidoreductase Activity ◽  
Site Of Action ◽  
Synthetic Steroids

ABSTRACT Six different steroidal analogues with previously suggested effects on gonadal Δ5,3β-hydroxysteroid oxidoreductase, 17α-hydroxylase and C17-20 lyase were investigated in vitro and in vivo. Testicular microsomal conversion of dehydroepiandrosterone to androstenedione and testosterone and of pregnenolone to progesterone and 5α-pregnane-3,20-dione was used as an index of Δ5,3β-hydroxysteroid oxidoreductase activity. 17α-hydroxylase activity was estimated from testicular microsomal formation of 17α-hydroxyprogesterone, androstenedione and testosterone from progesterone and the activity of C17-20 lyase was determined from the conversion of 17α-hydroxyprogesterone into androstenedione and testosterone. Analysis by gas-liquid chromatography – mass spectrometry of the steroidal excretion patterns in urine and faeces from female rats treated with two inhibitors of 17α-hydroxylase and C17-20 lyase in vivo, (I) 16β-bromo-3β,17α-dihydroxy-5α-pregnane-11,20-dione and (II) 17β-ureido-1,4-androstadien-3-one, and a third inhibitor (VI) 17α-cyano-5-androstene-3β,17β-diol, which also inhibits Δ5,3β-hydroxysteroid oxidoreductase in vitro, demonstrates the absence of C19 steroids of ovarian origin. C19 steroids are not excreted by rats treated with I and II up to 7 days after the last dose suggesting that the effects of these inhibitors are persistent. Two other steroids (III) 17-cyano-5,16-androstadien-3β-ol 3-acetate and (V) 17-cyano-5,16-androstadien-3β-ol, inhibit Δ5,3β-hydroxysteroid oxidoreductase in vitro in addition to 17α-hydroxylase and C17-20 lyase and cause the abnormal appearance of Δ5,3β-hydroxy-C19 steroids in the urines of normal and adrenalectomized females but not in those of ovariectomized or in ovariectomized and adrenalectomized rats. Each of these inhibitors also eliminates urinary 3α,17α-dihydroxy-5α-pregnan-20-one of ovarian origin. The pattern of C21O4 and C21O5 steroids of adrenal origin was only slightly affected or not affected at all by I–III and V and VI. The steroidal excretion patterns obtained in treated animals indicate a predominantly ovarian site of action of these inhibitors in vivo. Thus, the present results indicate three agents which block sex hormone production in the rat and two which inhibit gonadal Δ5,3β-hydroxysteroid oxidoreductase with moderate or no inhibition of the adrenal excretion.

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