Calcium absorption in diphosphonate-treated rats: effect of parathyroid function, dietary calcium and phosphorus.

1. The role of parathyroid hormone (PTH) and 1, 25-dihydroxy-cholecalciferol (1,25-(OH)2D3) in modulation of intestinal Ca absorption was studied in rats, using disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), which is known to reduce 1,25-(OH)2D3 formation. 2. EHDP decreased intestinal Ca absorption. This effect could be abolished by small amounts of 1,25-(OH)2D3, whereas even large doses of PTH were ineffective. EHDP also decreased Ca absorption in thyroparathyroidectomized (TPTX) rats. Therefore the effect of EHDP on 1,25-(OH)2D3 production is unlikely to be mediated through PTH. 3. The correction by PTH of the decreased Ca absorption in TPTX rats was inhibited by EHDP. Since EHDP inhibits formation of 1,25-(OH)2D3 the effect of PTH on Ca absorption is likely to be mediated through this vitamin D3 metabolite. 4. In normal rats both a low Ca and a low P diet stimulated Ca absorption. In EHDP-treated intact rats low Ca still stimulated Ca absorption, whereas the effect of low P abolished. This indicates that low Ca and low P diets affect Ca absorption through different mechanisms. 5. Intestinal adaptation to a low Ca diet was still observed in EHDP-treated TPTX rats. Thus, in the rat, intestinal adaptation to low Ca diet can occur without PTH.     

EHDP-induced rachitic syndrome in rats is not reversed by vitamin D metabolites

To examine whether either of the two known active vitamin D metabolites 1,25(OH)2D3 or 24,25(OH)2D3 could reverse the mineralization defect induced by 1-hydroxyethylidene-1,1-bis phosphonate (EHDP), a model of EHDP-induced rickets was used. Rats at the age of 31 days were injected for 10 consecutive days with EHDP (10 mg/kg). Other littermates were treated with a combination of EHDP and either 1,25(OH)2D3 or 24,25(OH)2D3 or were treated following 10 days of EHDP, with either of the vitamin D metabolites for an additional 72 hr. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscope studies of growth plate cartilage and bone. EHDP-treated rats revealed signs of typical rickets, manifested by widened growth plates and impaired bone mineralization. Transmission electron microscope (TEM) examination revealed matrix vesicles distributed throughout the growth plate; however, there appeared to be an arrest of the spread of the crystals at the provisional zone of calcification. Treatment with either 1,25(OH)2D3 or 24,25(OH)2D3 failed to reverse the rachitic condition of the animals. Serum calcium blood levels were elevated in the 1,25(OH)2D3 and EHDP-treated group. 1,25(OH)2D3 and 24,25(OH)2/D3 further increased the already elevated serum alkaline phosphatase levels observed in EHDP rats, although the increase observed with 1,25(OH)2D3 was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal handling of calcium: influence of parathyroid hormone and 1,25-dihydroxyvitamin D3.

The influence of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the renal Ca handling was studied in vitamin D-replete rats. The relation between plasma concentration ([Ca]P) and urinary Ca (UCaV/ml GF) was ascertained by clearance techniques over the [Ca]P range of 1.4-3.4 mM varied by infusion of Ca gluconate. Chronic thyroparathyroidectomy (TPTX) decreased the plasma Ca threshold from about 2.3 to 1.5 mM. Between [Ca]P 1.4 and 3.4 mM there was a linear increase in UCaV/ml GF corresponding to 35-50% of the increment in filtered load. In TPTX, PTH (2.5 IU/h i.v.) shifted the Ca threshold from 1.5 to 2.3 mM, without changing the slope of UCaV/ml GF on [Ca]P. The effect of TPTX on the renal Ca handling was not corrected by doses of 1,25(OH)2D3, which increased the intestinal Ca absorption of TPTX rats to normal level. In intact and TPTX rats disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given at doses which inhibit the production of 1,25(OH)2D3 did not change the tubular Ca handling. Furthermore, 1,25(OH)2D3 had no effect in EHDP-treated TPTX rats. Therefore, tubular Ca handling does not appear to be altered in response to chronic endogenous variation or physiologic supplementation of 1,25(OH)2D3 in vitamin D-replete rats. This is in contrast to the marked alteration observed after TPTX or PTH administration.     

Regulation of Na-dependent phosphate influx across the mucosal border of duodenum by 1,25-dihydroxycholecalciferol

Animals treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), at doses which decrease the renal production and/or the plasma levels of 1,25-dihydroxycholecalciferol [1,25(OH)₂D₃], display a reduced net absorption of phosphate. In this study we investigated whether EHDP-treatment and administration of 1,25(OH)₂D₃ to EHDP-treated animals affected the phosphate influx across the mucosal border of rabbit duodenum. The initial rate of phosphate influx into mucosal cells was measured in isolated intestine. In control, untreated rabbits, the phosphate influx shows a saturable, Na-dependent component and a diffusional, Na-independent uptake. In tissue from rabbits treated for 3 days with EHDP, the phosphate influx was found to be strongly reduced. EHDP-treatment decreased the Na-dependent, carrier mediated phosphate influx in duodenum. Administration of 1,25(OH)₂D₃ to EHDP-treated animals reversed the reduced phosphate influx. These effects were mainly apparent through changes in theJ _mc ^max of the phosphate influx, which was decreased from 211±38.7 nmole/cm² h in controls to 42.1±18.1 nmole/cm² h in the EHDP-treated group and increased to 413±43.6 nmole/cm² h by 1,25(OH)₂D₃. The treatment did not appear to affect the diffusional, Na-independent phosphate influx. EHDP-treatment did not affect the influx of alanine in this segment suggesting that EHDP-treatment affects only 1,25(OH)₂D₃-dependent transport mechanisms. The results suggest that 1,25(OH)₂D₃ modulates the number of carrier sites available at the mucosal membrane for Na-dependent phosphate entry.     

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

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 ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed a low calcium diet.

The long term (70 days) effects of administering ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 mg. per kg. per day) on parathyroid function was investigated in pregnant cows fed a low calcium diet. Serum calcium and phosphorus were significantly lower at parturition and postpartum in EHDP-treated cows compared to pregnant control cows fed the low calcium diet. Plasma immunoreactive parathyroid hormone levels were similar prepartum, at parturition, and postpartum in cows administered EHDP and control cows. Immediately available calcium reserves were greater preparation in control cows than in cows receiving EHDP as indicated by a more rapid rate of return of serum calcium toward normal levels following ethylenediaminetetraacetic acid (EDTA)-induced hypocalcemia approximately 10 days prepartum. EHDP-treated cows responded to the hypocalcemic challenge with similar changes in plasma immunoreactive parathyroid hormone levels as in control cows; however, urinary hydroxyproline excretion increased at certain intervals only in control cows. Ultrastructurally, chief cells in parathyroid glands of both groups of cows were in an active stage of the secretory cycle with well developed organelles concerned with hormonela synthesis. Chief cells in cows administered EHDP were degranulated and contained fewer secretory granules in response to the hypocalcemia than those in control cows. Chief cells in EHDP-treated cows often had prominent perinuclear accumulations of microfilaments, scattered vacuolated mitochondria, and lysosomal bodies in the cytoplasm. Thyroid C-cells were densely granulated and thyroid calcitonin content was similar in both groups of cows. The principal defect in calcium homeostasis of EHDP-treated cows appeared to be an impairment both in bone calcium mobilization and bone matrix catabolism in response to the secretion of parathyroid hormone. In vitro uptake of 45Ca by duodenal mucosa and urinary excretion of cyclic adenosine monophosphate were similar in both groups of cows. The ability of the parathyroid glands to synthesize and secrete parathyroid hormone in response to hypocalcemia induced either by EDTA or associated with parturition was not impaired by the administration of EHDP.     

The effect of vitamin D treatment on decreased levels of ATP and energy charge in the thoracic aorta of uraemic rats

The contents of ATP, ADP, AMP and calcium in the thoracic aorta were determined in rats with moderate uraemia, and in rats with the same degree of uraemia following treatment with 1,25-dihydroxycholecalciferol (1,25-DHCC). The contents of ATP, ADP and total nucleotides were decreased in the thoracic aorta in the uraemic rats but not in uraemic rats following 1,25-DHCC treatment. The content of calcium in the aorta increased substantially in uraemic rats given 1,25-DHCC. The results indicate that the development of arterial calcifications in uraemic rats following vitamin D treatment is dissociated from an impaired energy metabolism, since vitamin D may simultaneously restore impaired energy metabolism and accumulate calcium in the aortic wall.     

The effect of vitamin D treatment on decreased levels of ATP and energy charge in the thoracic aorta of uraemic rats.

The contents of ATP, ADP, AMP and calcium in the thoracic aorta were determined in rats with moderate uraemia, and in rats with the same degree of uraemia following treatment with 1,25-dihydroxycholecalciferol (1,25-DHCC). The contents of ATP, ADP and total nucleotides were decreased in the thoracic aorta in the uraemic rats but not in uraemic rats following 1,25-DHCC treatment. The content of calcium in the aorta increased substantially in uraemic rats given 1,25-DHCC. The results indicate that the development of arterial calcifications in uraemic rats following vitamin D treatment is dissociated from an impaired energy metabolism, since vitamin D may simultaneously restore impaired energy metabolism and accumulate calcium in the aortic wall.     

Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.

Previous studies have shown that recombinant interferon gamma (IFN-gamma), crude T cell supernatants, or appropriate T-cell lines can cause total inhibition of the growth of M. tuberculosis inside murine peritoneal macrophages. In similar experiments with human monocytes much smaller effects are seen. This could be due to the relative immaturity of these cells. Because dihydroxy vitamin D3 (1,25-(OH)2 D3) can cause phenotypic differentiation of immature leukemic lines into macrophage-like cells, we have explored the possibility that exposure to cholecalciferol metabolites in vitro might increase the ability of monocytes to control proliferation of M. tuberculosis, or cause monocytes to mature into cells able to respond appropriately to IFN-gamma. Incubation of monocytes with three cholecalciferol metabolites induced anti-tuberculosis activity to an extent that correlated with their binding affinities to the intracellular receptor protein for the derivatives. 1,25-(OH)2 D3 also primed monocytes for phorbol myristate acetate-triggered reduction of nitroblue tetrazolium. The effects were additive rather than synergistic with those of IFN-gamma. Monocytes incubated with IFN-gamma developed 25-OH D3 1-hydroxylase activity, detected by conversion of tritiated 25-(OH) D3 to a more polar metabolite which coeluted with 1,25-(OH)2 D3 on straight and reverse-phase HPLC. The latter is a more active form in vivo. These findings help to explain claims for the efficacy of vitamin D in the treatment of some forms of tuberculosis, and also the occasional finding of raised serum calcium, and disturbed vitamin D metabolism in these patients.     

Vitamin D metabolism and function during pregnancy and the neonatal period

Recent evidence suggests that vitamin D plays an important role in calcium homeostasis during pregnancy and early extrauterine life. Vitamin D is metabolized by successive hydroxylations to 25-hydroxyvitamin D and then to 1,25-dihydroxyvitamin D, the most potent known metabolite of the vitamin. During pregnancy, the concentrations of this metabolite in maternal serum increase in parallel with the increased need to absorb dietary calcium. 1,25-Dihydroxyvitamin D is produced in the fetoplacental unit as well as in the maternal kidneys. Receptors for 1,25-dihydroxyvitamin D appear to be present in the placenta suggesting that the placenta may be a target for vitamin D action. Developmental changes in vitamin D metabolism and action have been documented in the neonate as well as in the mother and fetus. Clinical studies indicate that adequate vitamin D intake is important during pregnancy. Administration of vitamin D or its metabolites appears to be useful in the treatment of neonatal disorders.     

Physiological basis for absorptive and renal hypercalciurias.

Idiopathic hypercalciuria constitutes two major variants-absorptive hypercalciuria, characterized by a primary intestinal hyperabsorption of calcium, and renal hypercalciuria, in which renal tubular reabsorption of calcium is primarily impaired. The two forms of hypercalciuria may be distinguished from each other, since a) parathyroid function is stimualted in renal hypercalciuria, but normal or suppressed in absorptive hypercalciuria, b) the renal leak of calcium is present in renal hypercalciuria, but not in absorptive hypercalciuria, c) intestinal calcium absorption is probably increased primarily in absorptive hypercalciuria, and secondarily in renal hypercalciuria (from parathyroid hormone excess), d) the increased calcium absorption in renal hypercalciuria probably results from the parathyroid hormone-dependent stimulation of 1,25-dihydroxyvitamin D synthesis, whereas that in absorptive hypercalciuria may be vitamin D-independent, e) the response of the two conditions to certain treatments is unique, and f) the sequelae of parathyroid hormone excess, such as low bone density and negative calcium balance, may be present in renal hypercalciuria, but not in absorptive hypercalciuria. These findings provide a physiological basis for the consideration of absorptive and renal hypercalciurias as distinct and separate entities.     

Studies on dentinogenesis in the rat

Summary The effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) in vivo on crystal growth in the early stages of predentin calcification were studied in newborn Sprague-Dawley rats after intraperitoneal injection of 0.1 ml physiological saline solution containing EHDP at a concentration of 100 or 500 µg/ml. The animals were given one injection per day for four consecutive days, thus receiving a total amount of 8 or 40 mg EHDP respectively. Control rats were injected with the same volume of physiologic saline alone. The following electron microscope observations were made: In dentin, the EHDP-treated rats were found to exhibit crystallites of smaller size than the normal controls. In the mineralization zone, most of the needle-like crystallites did not reach 20 Å in width. Their further growth was inhibited, only a few reaching 25 Å in width in the intertubular dentin. Within extracellular membrane-bound bodies or dentinal globules normally found in early formed predentin matrix, needle-like crystallites appeared before mineral deposits were visible in the predentin matrix. The crystallites had a paired appearance with a central electron-lucid core. The crystallite pattern was disturbed in EHDP-treated rats. Although less pronounced, similar changes were found also in rats given the lower dose of EHDP.     

Comparative abilities of various metabolites of vitamin D to protect cultured human macrophages against tubercle bacilli

Vitamin D metabolites have several biologic functions besides the best-known one of controlling mineral metabolism, one of which may be protection against tuberculosis. The chemical structures of the metabolites govern their functions. The most potent metabolite for regulating calcium metabolism is 1,25(OH)2-vitamin D3 (1,25-D3). This metabolite also is able to protect cultured human monocytes and macrophages (MP) against tubercle bacilli (TB). To determine whether these two functions are connected, 14 other analogs or metabolites of vitamin D were compared with 1,25-D3 for ability to protect cultured MP against TB. Blood-derived MP from 18 different donors were used in 70 experiments. The MP were infected with TB, then incubated for 7 days in medium containing 4 micrograms/ml of metabolite or synthesized analog. Growth of TB in the MP was measured by colony-forming unit counts from samples of lysed MP at 0, 4, and 7 days after infection. The metabolites, none of which inhibited TB in the absence of MP, varied from unprotective to bacteriostatic in the MP. Four of them were nearly as protective as 1,25-D3, and the metabolite 25S, 26(OH)2-vitamin D3 was consistently more protective. An analog synthetically designed for maximum ability to promote cell differentiation was unprotective. There was no correlation between metabolite ability to protect and known ability to stimulate calcium mobilization. These results suggest that antituberculosis protection of human MP by vitamin D metabolites or analogs can be separated from their functions of inducing cell differentiation and controlling mineral metabolism.     

Regulation and function of the FGF23/klotho endocrine pathways

Calcium (Ca(2+)) and phosphate (PO(4)(3-)) homeostasis are coordinated by systemic and local factors that regulate intestinal absorption, influx and efflux from bone, and kidney excretion and reabsorption of these ions through a complex hormonal network. Traditionally, the parathyroid hormone (PTH)/vitamin D axis provided the conceptual framework to understand mineral metabolism. PTH secreted by the parathyroid gland in response to hypocalcemia functions to maintain serum Ca(2+) levels by increasing Ca(2+) reabsorption and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] production by the kidney, enhancing Ca(2+) and PO(4)(3-) intestinal absorption and increasing Ca(2+) and PO(4)(3-) efflux from bone, while maintaining neutral phosphate balance through phosphaturic effects. FGF23 is a recently discovered hormone, predominately produced by osteoblasts/osteocytes, whose major functions are to inhibit renal tubular phosphate reabsorption and suppress circulating 1,25(OH)(2)D levels by decreasing Cyp27b1-mediated formation and stimulating Cyp24-mediated catabolism of 1,25(OH)(2)D. FGF23 participates in a new bone/kidney axis that protects the organism from excess vitamin D and coordinates renal PO(4)(3-) handling with bone mineralization/turnover. Abnormalities of FGF23 production underlie many inherited and acquired disorders of phosphate homeostasis. This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts.     

Electron microscopic cytochemical localization of a basolateral calcium adenosine triphosphatase in vitamin D replete chick enterocytes

A cytochemical technique for the electron microscopic localization of calcium adenosine triphosphatase (Ca-ATPase) was utilized to localize this enzyme in the enterocytes of rachitic and vitamin D-replete chicks. In animals treated with cholecalciferol (CC, vitamin D3), an electron-dense reaction product was located along the basolateral membranes of the absorptive cells within 72 hr after injection. Similarly, a reaction product was identified in association with the basolateral membranes within 24 hr after injection of 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D. A microvillar reaction product was not seen in either of these two groups. Electron-dense reaction products were also seen in association with mitochondria and scattered throughout the cytoplasm of these enterocytes. The Ca-ATPase reaction product was dependent upon the presence of medium calcium and substrate (ATP), was inhibited by vanadate, and was heat labile. In the rachitic animals, a reaction product indicative of Ca-ATPase activity was not seen in association with either the basolateral membranes or the mitochondria. These data appear to indicate that an energy-requiring calcium-activated membrane pump plays a role in the flux of calcium across the enterocytes of the small intestine.     

Calcium transport in small intestine during pregnancy and lactation

The factors involved in calcium homeostasis during the mammalian reproductive cycle and specifically in the control of active calcium transport in the intestine have not been thoroughly investigated. For this reason calcium transport in the intestine was measured in vitamin D-replete and vitamin D-deficient rats during pregnancy and lactation using the everted gut sac technique. In addition the changes in the plasma concentrations of calcium and 1,25-dihydroxyvitamin D were measured and correlated with transport. During the later stages of pregnancy and during lactation, the concentration of calcium in the plasma is reduced 10-30%. In turn, in the vitamin D-replete rat, the concentration of 1,25-dihydroxyvitamin D in the plasma increases from a control value of 26 pg/ml to 158 pg/ml at day 14 of lactation. Calcium transport in the intestine increases late in pregnancy, peaks during lactation, and then falls to control values by 3 wk postweaning in both vitamin D-replete and D-deficient animals. These findings strengthen the established relationship between 1,25-dihydroxyvitamin D and active calcium transport in the intestine as well as suggest that some factor(s) independent of vitamin D is stimulating intestinal calcium transport during the reproductive cycle.     

去卵巢骨质疏松模型大鼠小肠钙结合蛋白mRNA表达与菟丝子黄酮的干预

背景：菟丝子是旋花科植物菟丝子Cuscutachinensis Lam.的成熟种子,为温补肾阳的要药,前期研究表明,由菟丝子组成的补肾复方在抑制骨量丢失,改善骨密度方面有明显疗效。 目的：探讨菟丝子黄酮对去卵巢骨质疏松模型大鼠股骨骨密度、血清和肾脏1,25-二羟基维生素D3(1,25(OH)₂ D₃)含量、小肠钙结合蛋白(CaBp-D9K)mRNA表达的影响。 方法：72只SD雌性大鼠,随机数字表法均分为6组(n=12)：假手术组、模型组、维生素 D3组和菟丝子黄酮小、中、大剂量组。假手术组仅行假手术,其余5组分别行卵巢切除,1周后分别灌胃给予维生素D3 (2 mg/kg)以及小、中、大剂量菟丝子黄酮连续给药3个月。腹主动脉取血,分离血清,取出肾脏,采用酶联免疫吸附法检测 1,25(OH)₂ D₃含量。之后处死动物,取出股骨,测定骨密度;取出第2腰椎,采用实时荧光反转录聚合酶链反应(real-time RT-PCR)测定腰椎和肾脏组织维生素D受体mRNA表达。取出小肠,采用RT-PCR测定小肠CaBp-D9K mRNA表达。 结果与结论：与假手术组相比,模型组股骨骨密度、血清和肾脏 1,25(OH)₂ D₃、腰椎组织维生素D受体mRNA、小肠CaBp-D9K mRNA表达均下降。与模型组比较,菟丝子黄酮中、大剂量组和维生素D3组均可使股骨骨密度、血清和肾脏1,25(OH)₂ D₃、腰椎组织维生素D受体mRNA、小肠CaBp-D9K mRNA表达增加。菟丝子黄酮能够显著提高去卵巢大鼠股骨骨密度、血清和肾脏1,25(OH)₂ D₃、腰椎组织维生素D受体mRNA、小肠CaBp-D9K mRNA表达,促进肠钙吸收与成骨细胞活性,增强骨质量。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

Rapid stimulation of calcium uptake by isolated rat enterocytes by 1,25(OH)2D3

Evidence is accumulating that 1,25(OH)2D3 may stimulate calcium transport from the intestinal lumen extremely rapidly by a mechanism which appears independent of de novo protein synthesis. To investigate this rapid action of 1,25(OH)2D3, the rate of calcium uptake by isolated enterocytes from duodena of young rats was determined in vitro as the uptake of⁴⁵Ca from 1–15 min. Prior in vitro exposure of cells to 1,25(OH)2D3 (100 pM) for 20 min significantly increased the rate of calcium uptake (p<0.001), an effect unaltered by 50 M cycloheximide. Incubation with 100 pM 1-alpha-hydroxyvitamin D3 produced the same effect (p<0.01). In contrast, exposure to 10 pM 1,25(OH)2D3, as well as to 100 pM or to 1,000 pM 25-hydroxyvitamin D3 induced no significant change. Because both 1,25(OH)2D3 and starvation may stimulate key enzymes in polyamine metabolism, we investigated the effects of (i) difluoromethyl-ornithine (CHF2-Orn), a specific irreversible inhibitor of ornithine decarboxylase and (ii) varying the timing of feeding prior to sacrifice. Both in vitro CHF2-Orn and feeding prior to sacrifice significantly decreased the baseline rate of calcium uptake (p<0.05) and reduced the effect of 1,25(OH)2D3. Increased duration of starvation significantly increased the baseline rate of calcium uptake (p<0.02) without changing the increment in rate of calcium uptake induced by 1,25(OH)2D3. The study suggests (i) that the early action of 1,25(OH)2D3 on the influx process of intestinal calcium transport may involve a different molecular specificity from that involved in the genomic action of 1,25(OH)2D3 and (ii) that changes in polyamine metabolism may play a part in this process.     

Calcium ATPase and intestinal calcium transport in uremic rats

Calcium ATPase, an enzyme involved in intestinal calcium transport, was measured in homogenates of duodenal mucosal scrapings of normal and uremic rats. The effects of calcium deprivation and treatment with 1 alpha,25-dihydroxycholecalciferol [1,25-(OH)2D3] were investigated as well. Uremia decreased the enzyme activity and impaired the rise after calcium deprivation as observed in intact rats. The 1,25-(OH)2D3 treatment increased the enzyme activity in uremic animals and resulted in an identical response to calcium deprivation as observed in intact rats; parathyroidectomy abolished this effect. A striking correlation between everted duodenal gut sac calcium transport and calcium ATPase activity could be demonstrated for all groups of rats studied. It is concluded that the calcium ATPase activity is linked to the production of 1,25-(OH)2D3 as well as to an additional factor, probably parathyroid hormone. The close relationship between enzyme activity and in vitro calcium transport, even during constant physiological supplementation with 1,25-(OH)2D3, suggests an autonomous role of the calcium ATPase activity for mediation of calcium transport in the duodenum in addition to the well-known mechanisms related to vitamin D and its metabolites.     

Cholecalciferol in ethanol-preferring rats muscle fibers increases the number and area of type II fibers

The chronic use of ethanol causes neuropathy and atrophy of type II fibers and promotes vitamin D decrease. This study evaluated cholecalciferol effects on the deep fibular nerve and extensor digitorum longus (EDL) muscle using an UChB ethanol-preferring rats model. Blood analyses were carried out to measure levels of 25-hydroxycholecalciferol (25(OH)D), calcium (Ca²⁺), Phosphorus (P), and parathyroid hormone (PTH). It was used EDL muscle to evaluate oxidative stress. The deep fibular nerve and EDL muscle were used for morphologic and morphometric assessment. 25(OH)D plasma levels were higher in the supplemented group and no alterations were observed in other parameters including the oxidative stress evaluation. The G ratio remained constant which indicates nervous conduction normality. Cholecalciferol supplementation promoted an increase in the number and area of type II fibers and a decrease in the area of type I fibers. In the studied model, there was neither alcoholic myopathy nor neuropathy. The EDL muscle glycolytic patterns in the high-drinker UChB rats may be associated with the differential effects of cholecalciferol on metabolism and protein synthesis in skeletal muscle.