Intestinal calcium transport

Vitamin D withdrawal is an obvious treatment for D toxicity (219). However, because of the 5—7 d half-life of plasma vitamin D and 20—30 d half-life of 25-hydroxy vitamin D, it may not be immediately successful. A prompt reduction in dietary calcium is also indicated to reduce hypercalcemia. Sodium phytate can aid in reducing intestinal calcium transport. Calcitonin glucagon and glucocorticoid therapy have also been reported to reduce semm calcium resulting from D intoxication (210). 

ARJMANDI B H, KHALIL D A and HOLLIS B w (2000) Ipiiflavone, a synthetic phytoestrogen, enhances intestinal calcium transport in vitro. Calcif Tissue Int 67, 225-29. 

Bronner F, Pansu S, Stein WD. 1986. An analysis of intestinal calcium transport across the rat intestine. Am J Physiol 250 G561-G569... 

Glucocorticoid hormones alter bone mineral homeostasis by antagonizing vitamin D-stimulated intestinal calcium transport, by stimulating renal calcium excretion, and by blocking bone formation. Although these observations underscore... 

Calcifediol (25[OH]D3) may also be used to advantage. Calcifediol is less effective than calcitriol in stimulating intestinal calcium transport, so that hypercalcemia is less of a problem with calcifediol. Like dihydrotachysterol, calcifediol requires several weeks to restore normocalcemia in hypocalcemic individuals with chronic renal failure. Presumably because of the reduced ability of the diseased kidney to metabolize calcifediol to more active metabolites, high doses (50-100 Pg daily) must be given to achieve the supraphysiologic serum levels required for therapeutic effectiveness. 

The USP XX (30) and the Official Methods of Analysis of the Association of Official Analytical Chemists (AOAC) (44) describe in detail the curative method more commonly known as the rat line method. This method is not applicable to products offered for poultry feeding. For poultry feeds, and fish liver oils and their extracts, the AOAC (44) also describes in detail the chick bone ash method. In addition to the above two methods, there is a method based on the comparative measurement of serum calcium in rats referred to as Intestinal Calcium Transport Assay and another method based on the comparative amounts of calcium absorbed by control and test chicken referred to as Calcium Absorption Test. These methods are described by DeLuca and Blunt (45). 

Initially, 25-OH-D3 was considered to be the main biologically active metabolite of vitamin D. But soon it was discovered that physiological concentrations of 25-0H-D3, like vitamin D3, are incapable of stimulating either intestinal calcium transport or bone calcium jnobilization (108-110). Earlier work (111,112) with [la- H] vitamin D3 had shown that one of the unknown metabolites had lost its tritium from the C-l position. Fraser and Kodicek (113) established that this active metabolite is 1-oxygenated 25-OH-D3 and that it was produced in the kidney. A short time later Lawson et al. (114) identified this metabolite to be la, 25-dihydroxyvitamin D3 (1,25-(0H)2D3) which was confirmed by other investigators (115,116). 

Some recent studies [19-21] suggest that not all of the actions of l,25(OH)2D3 are explained by l,25(OH)2D3 receptor interactions with the genome. Rapid effects of l,25(OH)2D3 on stimulating intestinal calcium transport have been demonstrated which occur too quickly (within 4-6 minutes) to involve genome activation and have led to the hypothesis that some of the actions of l,25(OH)2D3 may be mediated at the membrane or by extranuclear subcellular components. 

Schiff, H., and Binswanger, U., Calcium ATPase and intestinal calcium transport in uremic rats. Am. Physiol. Soc. 238, G424-G428 (1980). 

Assay for intestinal calcium transport and in vivo bone mobilization... 

The activities of la,25(OH)2D4 on a calcium transport and bone mobilization in vitamin D deficient SD rats were less than (about 1/2) those of la,25(OH)2D3. This is well understood by stronger affinity of la,25(OH)2D4 for DBP than that of la,25(OH)2D3 because of the decreased availability for target cells (decreased uptakes into the cells)[43,44], The hypercalcemic activities of 24-epi-la,25(OH)2D2 and la,25(OH)2D7 were negligible as compared with that of la,25(OH)2D3. Their effects on intestinal calcium transport was significantly smaller than that of la,25(OH)2D3 and it is required 10 fold more of these compounds to produce a similar activity to la,25(OH)2D3 [35]. 

Beonnee F (1990) Intestinal calcium transport the cellular pathway. Miner Electrolyte Metab 16 94-100. 

Peerenboom H, Keck E, Kruskemper HL and Strohmeyer G (1984) The defect of intestinal calcium transport in hyperthyroidism and its response to therapy. J Clin Endocrinol Metab 59 936-940. 

Of particular Importance is the recent observation that l,25-(OH)2D2 stimulates intestinal calcium transport In a complex blphaslc manner. 

An injection of l,25-(OH) D- causes a rapid rise in calcium transport to a peak value at 6 hours, followed by a decline to a low value at 12 hours, and a rise to a second maximum at 24 hours, which is sustained for several days. A second injection of l,25-(OH)2D2 after the 24-hour period results in a super-induction of the initial response in addition to the second response. These findings suggest that there are at least two mechanisms of intestinal calcium transport responsive to 1,25-(0H)2D2. The first response undoubtedly represents the transport activity of existing villus cells, whereas the second response likely results from an effect of 1,25-(OH)2D, on the crypt cells that then differentiate and migrate up the villus region to promote intestinal calcium transport. A similar blphasic response has been observed for... 

This section will be restricted to intestinal calcium transport, since it represents the focus of current efforts to understand the mechanism of action. Much work has been done to demonstrate the existence of a macromolecule that binds l,25-(OH)2D2 in the target tissues. Both chick and mammalian intestines contain a protein sedjyenting at 3.2 to 3.7 S that binds 1,25-(OH)2H2 ith a of 5 x 10 M.9 The association and dissociation rate constants have been... 

A major problem in explaining intestinal calcium transport responses to 1,25-(OH)20 is the lack of Information on the proteins or... 

The synthesis of 5,6-trans-25-hydroxycholecalciferol (376), a new vitamin D analogue, has been achieved. Treatment of 25-hydroxy-vitamin D3 (375) with iodine in light petroleum ether, followed by addition of Ne2S203 and chromatography, afforded 5,6-rra/j5-25-hydroxy-D3 (376), which has been shown to stimulate intestinal calcium transport. 

Synthesis of radioactive 25-OH-D3 allowed a pursuit of its metabolites and it was soon demonstrated that the polar metabolite of the small intestine, designated as peak V in the Wisconsin laboratories, peak p in the Cambridge laboratories, and 4B in the Riverside laboratories, was formed from 25-OH-D3 , Although Myrtle, Haussler and Norman fust reported marked biological activity of the intestinal metabolite, this finding could not be uniformly reproduced l Haussler et al. discovered that the intestinal metabolite initiated intestinal calcium transport very... 

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