Calcemic effects

Some of the resulting compounds, in particular the 22(S)-hydroxy-falecalcitriol, exhibit an excellent selectivity, with a very high activity on human carcinoma lines (HT-29) and no calcemic effect, as assessed in vivo on rats [156],... 

SchwUle PO, Scholz D, Samberger NM, Kayser PE. Studies ou the calcemic effect of iutraveuous secretiu iu humaus. Acta Hepatogastroeuterol (Stuttg) 1975 22(3) 192-200. 

The vitamin D receptor (VDR/NR1I1) is a member of the superfamily of steroid hormone receptors. It regulates calcium homeostasis, cell proliferation, and differentiation, and exerts immunomodulatory and antimicrobial functions [119]. VDR binds to and mediates the calcemic effects of calcitriol (la,25-dihydroxy vitamin D3) after forming an heterodimer with RXR. la,25-dihydroxyvitamin D3 negatively regulates its own synthesis by repressing the 25-hydroxyvitamin D3 la-hydroxylase (CYP27B1) in a cell-type selective event that involves different combinations of multiple VDR response elements [120, 121]. 

Parathyroid hormone can be assayed by its phosphaturic effect in mice (D2), its calcemic effect in parathyroidectomized rats (Dl, Mil), its effect on serum calcium in the dog (Ul), and its effect on the excretion of isotopic calcium or phosphate in the urine after the labeling of rats with Ca or P (C8, C9). None of these methods is particularly sensitive, and for this reason little work has been done on the estimation of parathyroid hormone in biological fluids. An attempt has been made to meas-... 

The bone resorbing activities of la,25(OH)2D2 and la,25(OH)2D4 were almost the same as for la,25(OH)2D3. It is positively related to binding affinity to VDR. The results clearly explain that the calcemic effects of la,25(OH)2D2 and la,25(OH)2D4 are comparable to that of la,25(OH)2D3 as expected from their binding affinity for VDR. Sato et al. reported that bone calcium mobilization of 24-epi-la,25(OH)2D2 and la,25(OH)2D7 in vitamin D deficient rats was about 50% of that by la,25(OH)2D3 by assessing serum calcium changes after intravenous administration [36]. The results of biological activities of la,25-(OH)2D analogues were shown in Table 1 in comparison with those of l,25(OH)2D3. 

Ca2 -chelators (B) prevent the enzymatic activity of Ca2+-dependent factors they contain COO groups that bind Ca2+ ions (C) citrate and EDTA (ethylenediaminetetraace-tic acid) form soluble complexes with Ca2+ oxalate precipitates Ca2+ as insoluble calcium oxalate. Chelation of Ca2+ cannot be used in vivo for therapeutic purposes because Ca2 concentrations would have to be lowered to a level incompatible with life (hypo-calcemic tetany). These compounds (sodium salts) are, therefore, used only for rendering blood incoagulable outside the body. This effect can be reversed at any time by addition of Ca2 ions. 

Recent studies have suggested that N-terminal-truncated PTH may be biologically active. Synthetic PTH(7-84), used as the available representative of N-terminal-truncated PTH, decreased serum calcium antagonized the calcemic, phosphatemic, and phosphaturic effects of intact PTH in thyroparathyroidectomized animals and was bound by a C-terminal PTH receptor distinct from the PTH/PTHrP receptor. ... 

The effects of thyrocalcitonin in reducing the serum levels of calcium and phosphate, and in increasing the output of phosphate in the urine, have not at present been shown to be significantly influenced by any hormone other than parathormone. Milhaud ef al. (M8) found that neither the thyrocalcitonin content of the thyroid gland nor the hypo-calcemic activity brought about by administration of thyrocalcitonin was significantly altered by hypophysectomy. The presence or absence of the thyroid gland, and therefore of thyroid hormone, does not appear to influence the sensitivity of an animal to thyrocalcitonin administration, while the interrelationship, if any, to suprarenal cortical activity does not appear to have been studied as yet. 

A general limitation for systemic application of l,25(OH)2D3 is its calcemic side-effects. Therefore, topical application, e.g. by calcipotriol, a significantly less calcemic analog of l,25(OH)2D3, is used for the treatment of psoriasis so far [47,179-182]. The... 

The parathyroid hormone regulates ionic calcium homeostasis in extracellular fluids by a direct action on the skeleton. It also promotes the renal excretion of phosphorus and produces other physiological effects which are not obviously related to its calcemic action. 

The fall in serum calcium which follows parathyroidectomy is associated with a rise in calcium excretion (T1). Taken in conjunction with the hypocalcemic hypercalcuria of clinical hypoparathyroidism (L5), this suggests that the apparent calcuric effect of parathyroid extract is simply a reflection of its calcemic action. In fact, administration of the hormone appears if anything to reduce urinary calcium. Evidence to this effect has been produced by Bernstein et al. (B6), who have demonstrated a steep rise in calcium/inulin clearance ratio in dogs after parathyroidectomy... 

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