Actinomycin D effect on lag in vitamin D-mediated calcium absorption in the chick

Norman, A. W.

doi:10.1152/ajplegacy.1966.211.3.829

Cited by 79 publications

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“…Vitamin D is believed to function in the regulation of calcium absorption from the gut by controlling the expression of genetic information (1,2). Several groups hypothesize that vitamin D induces the synthesis of mRNA and a special protein(s) that comprises part or all of a calcium transport system in the intestinal mucosa cell.…”

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confidence: 99%

A Rapidly Acting Metabolite of Vitamin D ₃

Haussler

Boyce

Littledike

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

141

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A vitamin D, metabolite in intestine more polar than 25-hydroxy-vitamin Vitamin D is believed to function in the regulation of calcium absorption from the gut by controlling the expression of genetic information (1, 2). Several groups hypothesize that vitamin D induces the synthesis of mRNA and a special protein(s) that comprises part or all of a calcium transport system in the intestinal mucosa cell. A calcium-binding protein induced by vitamin D has been isolated from the chick gut (3), and the vitamin has been shown to increase strikingly the Ca++-ATPase (4) and alkaline phosphatase (5) activity of intestinal microvillar membranes.Another important notion is that vitamin D must be metabolized prior to its functioning to induce calcium transport in the intestine. DeLuca and coworkers (6, 7) have isolated from blood a vitamin D3 metabolite which is 1.4 times as active as native vitamin D3. They determined the structure of this compound to be 25-hydroxy-vitamin D3(25-OH D3) and proposed that it was the active form of vitamin D3 (8, 9). Norman and associates (10) and later Kodicek and collaborators (11) used silicic-acid chromatography to detect a metabolite in chick intestine that was more polar than 25-OH D3. Haussler et al. (12) demonstrated that this metabolite was selectively associated with the nuclear chromatin of the target intestine and, more specifically, to a protein receptor molecule that was not a histone (13).In the present experiments, countercurrent distribution is employed to confirm the existence of a vitamin D3 metabolite in the intestine more polar than 25-OH D3. Isolation and biological assay of this metabolite reveals that it is the most efficacious and rapidly functioning metabolite of vitamin D3 yet tested and is, therefore, probably the active form of the vitamin in the chick intestine. Norman. Extraction techniquesLabeled steroids were administered dissolved in 1,2-propanediol. The chicks were killed by decapitation; the blood was collected with the aid of a funnel and the small intestine excised immediately. Intestinal-mucosa chromatin was prepared as described (12) and either the chromatin, whole intestine, or plasma was extracted with organic solvents by a modification of the procedure of Bligh and Dyer (14). The lipid extract was dried under N2 in preparation for countercurrent distribution. Countercurrent distribution (CCD) Distribution studies were carried out on an H.O. Post, model no. 2-B,100-tube automated machine; 100 transfers were performed with a 10-ml mobile (upper) phase and a 10-ml stationary (lower)phase. Solvent system 1: ethyl acetate-hexaneethanol-water 5:15:11:9 or 2: same solvents 5:15:7.5:12.5 were used.Metabolite from 1250 chick guts Triton X-100-washed chromatin (12) was isolated from the intestinal mucosa of all chicks 15-hr after an oral dose of 50 IU* of [3H]vitamin D3. The chromatin was washed with 10 mM Tris -HC1 (pH 7.5) to remove Triton, and then extracted with a total of 20 liters of acetone-dichloroethane 2:1 with the aid of a Waring blender. A...

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confidence: 99%

A Rapidly Acting Metabolite of Vitamin D ₃

Haussler

Boyce

Littledike

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

141

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“…The vitamin in nuclei would act on the synthesis (12,27). On the other hand, membrane bound vitamin D3 would act on the membrane permeability for calcium, and this process did not involve protein syn thesis, and was not influenced by actinomycin D. Zull et al (10) and Norman (28) reported that actinomycin D treatment did not alter the tissue distribution of a did of 2000 and 350IU of 3H-vitamin D3 in vitamin D deficient rats and chicks, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Norman (28) reported that the mini mum dose of vitamin D3 which would give a consistent response in the assay was found to be 3-5IU, but much larger responses could be obtained by the dose; of 100IU, approximately 4-5 fold stimulation in calcium absorption over the response given by vitamin D defi cient chicks. From these, the actinomycin D insensitive vitamin D3 action would be impor tant in calcium absorption.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Orally Administered 45Ca in Rat Intestinal Tissues and Vitamin D3 Effect

Moriuchi¹,

Watanabe²,

Hosoya³

1970

J. Vitaminol

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The effects of vitamin D3 and actinomycin D on the radioactive calcium distribution were studied in the rat intestinal mucosa and muscle 5 and 30 minutes after the oral administration of 45Ca.1. Serum 45Ca concentration at 30min was increased significantly in the vitamin D3 treated rat, and this vitamin D3 effect was inhibited by actinomycin D. The action of vitamin D3 and actinomycin D was not observed at 5min. 2. 45Ca was observed in the proximal parts of intestinal mucosa (from pyloric end to 30cm) at 5min, and at 30min it came to be observed in the distal (40-60cm). 45Ca in the proximal parts at 5min was reduced with vitamin D3, and actinomycin D did not seem to be influenced on this vitamin D3 action. 45Ca in the distal (at 30min) was enhanced with vitamin D3 and this action was partially inhibited by actinomycin D. 3. 45Ca in muscle was lower than in mucosa. Observed pattern of 45Ca distribution at 5min in muscle was not so different in vitamin D deficient and D3 treated rats. Actinomycin D did not exert its action on muscle at 5min. Distribution patterns of 45Ca in muscle at 30min were almost similar to the mucosal patterns.4. Subcellular distribution of 45Ca was observed in the duodenal mucosa. Nuclei and cell debris (brush borders) have relative amounts of 45Ca 5min after 45Ca administration. At 30 minutes, 45Ca of subcellular fraction was significantly decreased, especially in nuclei, cell debris and mitochondria.This reduction was moderated by vitamin D3. Actinomycin D inhibited this vitamin D3 action in microsomes and supernatants.From these results, it was suggested that calcium transport would be carried out in two ways, membrane permeable system (actinomycin D insensitive) and the system involving calcium carrier protein (actinomycin D sensitive).

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“…It is now believed that this vitamin induces the synthesis of the appropriate enzyme systems or the alteration of membrane structure necessary for calcium absorption (Norman 1966). Regarding the effect of vitamin D on bone calcification it has been stated that it seems unlikely that an additional effect of vitamin D at the calcification sites exists, but that the question remains still open (DeLuca 1967).…”

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“…Experimental data suggest, on the other hand, that vitamin D action on bone involves or requires a cellular component and it is not simply due to an acceleration of physicochemical exchange processes between crystal surface and extracellular fluid (Yuile et al 1967). In studies on Ca 45 absorption in the rachitic chick it was found that vitamin D exerts its action only after a lag time of several hours (Norman 1966). Evidence was also provided that vitamin D administration induces the formation or elaboration of a calcium binding factor by intestinal mucosa, and that this factor is a protein.…”

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confidence: 99%

Vitamin D and Skeletal Metabolism: Experimental Studies in the Rat

Sevastikoglou¹,

Ray²,

Hjertquist³

et al. 1970

Acta Orthopaedica Scandinavica

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References 73 82 FOREWORDThere are few topics in medicine, that have attracted the interest of so many investigators as the physiological significance(s) of Vitamin D. However, in spite of extensive research and innumerable publications, knowledge concerning the mode of action of the vitamin on the calcium homeostasis of the body is still incomplete.The complexity of the "simple question" how does vitamin D influence skeletal metabolism? defies a simple experimental solution and requires an integrated, multilevel approach. With this in mind the authors have during the last years tried to throw some light on the question by conducting a correlated series of experimental investigations. The study started in Chicago, Illinois, was continued in the Orthopaedic Research Laboratory in Uppsala and later in Umea, Sweden. The results were discussed at each stage by the senior authors (J. A. S. and R. D. R.) and each step was planned in close collaboration.The results of these studies reinforce certain previous findings under standard conditions not prevalent in the multitude of separate studies in separate laboratories by separate people in the past, and add new aspects on the mechanism of action of vitamin D on bone.The publication of the different sections of the work in the form of a supplementum was chosen since it gives a more coherent survey of the results obtained.The investigations were aided by grants from the U. S. Atomic Energy Commission, INTRODUCTIONRickets as a clinical entity was first reported in 1645 in a thesis by Whistler l ) entitled "De morbo puerili Anglorum quem patrio idiomate indigenae vocant, The Rickets". A detailed description of the disease followed 5 years later by Glison (1650). Almost two centuries later Guerin (1838) was probably the first to produce rickets in puppies and suggested that rickets resulted from a faulty diet. The curative effect of cod liver oil in clinical rickets was pointed out by Trousseau (1865). Hopkins in 1912 first suggested that rickets was due to a dietary deficiency and the same year Funk (1912) propounded the "vitamin hypothesis" according to which the existence of separate anti-beriberi, antiscurvy, anti-rachitic and anti-pellagra "vitamins" was postulated. Huldschinsky (1919) showed that rickets could be cured by artificial light no less than by direct sunlight. Steenbock and his co-workers, in 1924, deduced that ultraviolet rays activated some vitamin precursors in the skin of the body or in the food. Hess and Weinstock (1924) confirmed this shortly afterwards. One year later a crude cholesterol fraction was isolated from cod-liver-oil, by the same authors, and it was thought to be the "anti-rachitic provitamin". The vitamin itself was isolated, in a pure state, from the irradiation products of ergosterol by Askew et al. in 1930 and by Windhaus et al. in 1932. The vitamin was first named vitamin D or calciferol. Ergocalciferol was later adopted as its official name. Two calcemic sterols have been prepared in crystalline form, namely vitamin Dz or dihydrota...

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Actinomycin D effect on lag in vitamin D-mediated calcium absorption in the chick

Cited by 79 publications

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A Rapidly Acting Metabolite of Vitamin D ₃

A Rapidly Acting Metabolite of Vitamin D ₃

Distribution of Orally Administered 45Ca in Rat Intestinal Tissues and Vitamin D3 Effect

Vitamin D and Skeletal Metabolism: Experimental Studies in the Rat

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Actinomycin D effect on lag in vitamin D-mediated calcium absorption in the chick

Cited by 79 publications

References 0 publications

A Rapidly Acting Metabolite of Vitamin D 3

A Rapidly Acting Metabolite of Vitamin D 3

Distribution of Orally Administered 45Ca in Rat Intestinal Tissues and Vitamin D3 Effect

Vitamin D and Skeletal Metabolism: Experimental Studies in the Rat

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A Rapidly Acting Metabolite of Vitamin D ₃

A Rapidly Acting Metabolite of Vitamin D ₃