共查询到20条相似文献,搜索用时 0 毫秒
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John G. Haddad Jean Walgate Chong Min Theodore J. Hahn 《Biochimica et Biophysica Acta (BBA)/General Subjects》1976,444(3):921-925
Serum and post-microsomal supernatants of human lymphocyte, erythrocyte, skeletal muscle and parathyroid adenoma homogenates were examined for specific binding of 25-hydroxycholecalciferol (25-OHD3) and 1,25-dihydroxycholecalciferol (1,25-(OH)2D3). Muscle, lymphocytes and parathyroid adenomata extracts contained a 6-S 25-OHD3-binding protein which was not found in erythrocyte extracts, and which was distinct from the smaller serum transport α-globulin. A cathodal, 1,25-(OH)2D3-binding protein, which sedimented at 3–4 S was also detected in parathyroid tissue. These observations suggest the possibility of direct physiologic interaction between vitamin D metabolites and nucleated human tissues other than intestine and bone. 相似文献
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Early rise in cyclic GMP after 1,25-dihydroxycholecalciferol administration in the chick intestinal mucosa 总被引:2,自引:0,他引:2
cGMP and cAMP levels were measured in the duodenal mucosa of 12-day-old chicks that had been raised from hatching in vitamin D-depleting conditions and at the time of use were moderately hypocalcemic. After administration of a dose (250 ng) of 1,25-dihydroxycholecalciferol, the cGMP levels increased about twofold in 2–3 hr and returned to control levels between 4 and 6 hr. Our data suggest that 1,25-dihydroxycholecalciferol behaves like other steroid hormones which induce an early rise in cGMP in their respective target tissues. 相似文献
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Vitamin D-deficient chicks were injected intracardially with physiological doses of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) and the formation of intestinal brush-border proteins was followed in vitro. Within 4 h of receiving the hormone the incorporation of radioactive leucine into at least two proteins in the brush-borders was increased. The apparent molecular weights of these proteins were 45 000 and 84 000. The change in the synthesis of these proteins was followed with time and compared with the concomitant changes in intestinal calcium transport. The relationship of these changes is such that there is a strong possibility that the proteins are involved in calcium absorption. 相似文献
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Isolated chick kidney proximal tubule cells have been used in a study of the mechanism by which PTH inhibits Na+-dependent Pi transport in the kidney. Treatment with PTH inhibits Pi uptake by the cells by 13% and stimulates cyclic AMP production by 77%. Forskolin, a potent activator of adenyl cyclase, brought about an 11-fold stimulation of cyclic AMP production by the cells, but in contrast to PTH, the drug had no effect on Na+-dependent Pi uptake. These results provide evidence that PTH action on phosphate transport is not mediated by cyclic AMP. 相似文献
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Daniel D. Bikle E. Wayne Askew David T. Zolock Robert L. Morrissey Robert H. Herman 《生物化学与生物物理学报:生物膜》1980,598(3):561-574
We have evaluated the effect of vitamin D-3 and its metabolite 1,25-dihydroxyvitamin D-3 on Ca2+ accumulation by chick intestinal mitochondria. Ca2+ accumulation appears to occur in two phases: an early, transient accumulation into an Na+-labile pool followed by an ATP-dependent accumulation into an Na+-resistant pool. Ca2+ accumulation is extensive at free Ca2+ concentrations greater than 3 · 10?6 M in the presence of ATP. Ruthenium red and dinitrophenol block Ca2+ accumulation, but atractyloside does not. Oligomycin blocks ATP-supported accumulation completely with a partial inhibition of ATP and malate-supported accumulation. Little difference could be found in mitochondrial preparations from vitamin D-deficient chicks compared to those from vitamin D-3 (or 1,25(OH)2D-3)-supplemented chicks with respect to respiratory control, oxygen consumption, efficiency of oxidative phosphorylation, affinity for Ca2+, or the rate and extent of ATP-supported Ca2+ accumulation. Intestinal cytosol stimulated Ca2+ accumulation, but this was not specific with respect to vitamin D status or tissue of origin, nor was it duplicated by chick intestinal Ca2+-binding protein. 30 ng/ml 1,25(OH)2D-3 stimulated Ca2+ accumulation directly, regardless of the presence of intestinal cytosol. Other vitamin D metabolites were less potent: 25-hydroxyvitamin D-3 > 24,25-dihydroxyvitamin D-3 = vitamin D-3. Since increasing the free Ca2+ concentration from 3 · 10?6 to 1 · 10?5 M increased Ca2+ accumulation approx. 50-fold, whereas direct stimulation by 1,25(OH)2D-3 in vitro increased Ca2+ accumulation less than 2-fold, we conclude that 1,25(OH)2D-3 influences mitochondrial accumulation of Ca2+ in vivo primarily by altering cytosol concentrations of free Ca2+. 相似文献
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Kinetics of kidney mitochondrial 25-hydroxycholecalciferol-1 alpha-hydroxylase in vitamin D-repleted weanling guinea pigs 总被引:1,自引:0,他引:1
Kinetics of vitamin D-repleted guinea pig kidney mitochondrial 25-hydroxycholecalciferol-1 alpha-hydroxylase were studied. Omission of malate, source of mitochondrial reducing equivalents, abolished the 1 alpha-hydroxylase activity as well as the degradation of 1 alpha, 25-dihydroxycholecalciferol [1,25(OH)2D3], indicating that both functions shared elements of a common pathway. Preincubation of the mitochondrial preparation in presence of 10 nM 1,25(OH)2D3 for 15 min protected the labeled 1,25(OH)2D3 from degradation. Under these conditions an apparent Km of 605 nM and a Vmax of 40 pmol/30 min/mg mitochondrial protein were observed. These data show that this particular mammalian model may be used to study the modulation of mammalian 1 alpha-hydroxylase activity. 相似文献
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C. Tony Liang Janice Barnes Richard A. Balakir Bertram Sacktor 《The Journal of membrane biology》1986,90(2):145-156
Summary Thein vivo andin vitro effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on calcium uptake by isolated chick duodenal cells were studied.In vivo, 1,25-(OH)2D3 given orally to vitamin D-deficient chicks increased the initial rate of calcium uptake by cells prepared 1 hr after administration of the hormone. The rate was stimulated approximately 100%, 17 to 24 hr after repletion.In vitro, pre-incubation of 1,25-(OH)2D3 with cells from D-deficient chicks increased the cellular rate of calcium uptake in a concentration-dependent relationship. Enhancement was found with 10–15
m, was maximal at 10–13
m, and was diminished at higher (10–11
m) concentrations. Stimulation was observed after a pre-incubation period as brief as 1 hr. The potency order for vitamin D3 analogs was 1,25-(OH)2D3=1-(OH)D3>25-(OH)D3>1,24,25-(OH)3D3>24,25-(OH)2D3>D3. The maximal enhancement in calcium uptake induced by the analogs was the same, only the concentration at which the cell responded was different. The effectiveness of 1,25-(OH)2D3 was five orders of magnitude greater than D3. Kinetically, 1,25-(OH)2D3 increased theV
max of calcium uptake; the affinity for calcium (K
m=0.54mm) was unchanged. The enhanced uptake found after the cells were pre-incubated for 2 hr with the hormone was completely blocked by inhibitors of protein synthesis. 1,25-(OH)2D3,in vitro, also increased calcium uptake in cells isolated from D-replete chicks. The maximal rates of uptake were the same in cells from D-deficient and D-replete animals. The hormone had no effect of calcium efflux from cells. Calcium uptake in microvillar brush-border membrane vesicles was increased by 1,25-(OH)2D3. These findings suggest that thein vitro cell system described in this paper represents an appropriate model to examine the temporal relationships between 1,25-(OH)2D3 induction of calcium transport and specific biochemical correlates. 相似文献
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Yoshikazu Arai Yohei Kiyotsuka Kousei Shimada Kazunori Oyama Masanori Izumi 《Bioorganic & medicinal chemistry letters》2019,29(18):2613-2616
The discovery and optimization of a novel series of PTHR1 antagonists are described. Starting from known PTHR1 antagonists, we identified more potent 1,4-benzodiazepin-2-one derivatives by means of a scaffold-hopping approach. The representative compound 23 (DS08210767) exhibited nanomolar-level PTHR1 antagonist activity and potential oral bioavailability in a pharmacokinetic study. 相似文献
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Selective analogs of 1α,25-dihydroxyvitamin D3 for the study of specific functions of Vitamin D 总被引:1,自引:1,他引:0
Hector F. DeLuca Lori A. Plum Margaret Clagett-Dame 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):263
New analogs of 1α,25-dihydroxyvitamin D3 synthesized in our research group that show selective activity in vivo are presented along with supporting biological results. Compounds that act preferentially on intestine are 2-(3′-propylidene-19-nor-(20S or 20R))-1α,25-dihydroxyvitamin D3 and 2-methylene-19-21-dinor-1α,25-dihydroxyvitamin D3. Compounds that act anabolically to induce bone formation are 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD), the 2α-methyl derivative, the 26,27-dimethyl derivative, and the 26-dimethylene derivative. Compounds that act preferentially on parathyroid glands are 2-methylene-19-nor-1α-hydroxy-homopregnacalciferol, the 20S-bishomo derivative and the 2-methylene-19,26,27-trinor-1α,25-dihydroxyvitamin D3. These latter compounds do not elevate serum calcium until doses of the order of >300 μg/kg body weight are used, while parathyroid hormone levels are suppressed at much lower doses. Some of these novel analogs may ultimately be useful as new and safer therapeutic agents. Regardless of their clinical utility, they represent valuable research tools that can be used to study the specific functions of the Vitamin D hormone in vivo. 相似文献
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Ulf Diczfalusy Katarina E. Olofsson Ann-Margreth Carlsson Mei Gong Douglas T. Golenbock Olav Rooyackers Urban Fl?ring Harry Bj?rkbacka 《Journal of lipid research》2009,50(11):2258-2264
During screening of genes upregulated by lipopolysaccharide (LPS; endotoxin) treatment of bone marrow-derived mouse macrophages, it was unexpectedly found that cholesterol 25-hydroxylase (Ch25h) was strongly upregulated. Treatment of macrophages with 10 ng/ml of LPS for 2 h resulted in a 35-fold increase in the expression of Ch25h. In contrast, LPS treatment did not increase the expression of Cyp27a1 or Cyp7b1. The increased Ch25h expression was found to be independent of Myeloid differentiation protein 88 signaling but dependent on Toll-like receptor 4 signaling. LPS treatment of macrophages caused a 6- to 7-fold increase in cellular 25-hydroxycholesterol concentration. When macrophages were treated with increasing concentrations of 25-hydroxycholesterol, a dose-dependent release of CCL5 into the culture medium was observed. Intravenous injection of LPS in eight healthy volunteers resulted in an increase in plasma 25-hydroxycholesterol concentration. The possibility is discussed that 25-hydroxycholesterol may have a role in the inflammatory response, in addition to its more established role in the regulation of cholesterol homeostasis. 相似文献
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Toshio Matsumoto Yumiko Kawanobe Etsuro Ogata 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1985,845(3):358-365
Regulation of 25-hydroxyvitamin D-3 24-hydroxylase by 1,25-dihydroxyvitamin D-3 and synthetic human parathyroid hormone fragment 1–34 (PTH1–34) was investigated using a cloned monkey kidney cell line, JTC-12. Treatment of the cells with 1,25-dihydroxyvitamin D-3 markedly enhanced the conversion of [3H]-25-hydroxyvitamin D-3 into a more polar metabolite. The metabolite was identified as 24,25-dihydroxyvitamin D-3 by normal phase and reverse phase high-performance liquid chromatography and periodate oxidation. The 24-hydroxylae activity appeared to follow Michaelis-Menten kintics, and 1,25-dihydroxyvitamin D-3 treatment increased the of 24-hydroxylase from 33 to 95 pmol/h per 106 cells without affecting the apparent value of the enzyme (220 nM in control vs. 205 nM in 1,25-dihydroxyvitamin D-3 treated cells). The enzyme activity reached a maximum between 4 and 8 h of treatment with 1,25-dihydroxyvitamin D-3. The dose of 1,25-dihydroxyvitamin D-3 required to cause a half-maximal stimulation was about 3 · 10?10 M. The 1,25-dihydroxyvitamin D-3-induced increase in 24-hydroxylase was almost completely inhibited by the presence of 1 μM cycloheximide. Treatment of the cells with PTH1–34 caused a dose-dependent increase in cyclic AMP production. Half-maximal stimulation of cyclic AMP production was obtained at about 5 · 10?9 M PTH1–34. When 2.4 · 10?9 M PTH1–34 was added after 1,25-dihydroxyvitamin D-3 treatment, the 1,25-dihydroxyvitamin D-3-stimulated 24-hydroxylase was inhibited to of control. Higher concentrations of PTH1–34 caused less inhibition of the enzyme activity. When cyclic AMP was added instead of PTH1–34, the enzyme activity was also suppressed significantly. These results indicate that, in JTC-12 cells, 1,25-dihydroxyvitamin D-3 stimulates 24-hydroxylase in a dose- and time-dependent manner by increasing the of the enzyme through a mechanism dependent upon new protein synthesis, and suggest that PTH1–34 inhibits the 1,25-dihydroxyvitamin D-3-induced stimulation of 24-hydroxylase through its effect on cyclic AMP production. 相似文献
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David L. Carnes Constantine S. Anast Leonard R. Forte 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,629(3):546-552
Rats fed a diet deficient in both vitamin D and Ca2+ exhibited a greater depression of the renal parathyroid hormone (PTH)-dependent adenylate cyclase than was observed in rats fed diets deficient in either vitamin D or calcium. Total serum Ca2+ was decreased from a control level of 11.2 mg/dl to 8.5 mg/dl in rats fed the diet deficient in calcium alone, and to 5.4 mg/dl in rats fed the diet deficient in vitamin D. Serum calcium was decreased further to 4.3 mg/dl in rats fed the diet deficient in both vitamin D and Ca2+. Serum immunoreactive PTH was significantly elevated over control levels when rats were fed the test diets; however, there were no significant differences between the elevated levels in the three experimental groups. Repletion of rats deficient in vitamin D only with a single oral dose of 3200 I.U. vitamin D-2 resulted in restoration of serum calcium to normal levels, a return of serum PTH to the control state, and an associated increase in PTH-dependent adenylate cyclase activity to the control level by 72 h. Repletion of rats deficient in both vitamin D and Ca2+ with the same dose of vitamin D-2 raised serum Ca2+ to 7.2 mg/dl by 72 h, but did not cause a reduction in circulating PTH, nor did it result in any significant improvement in the responsiveness of the membrane adenylate cyclase to PTH. These results suggest that elevated PTH is a factor in the down regulation of the PTH-dependent adenylate cyclase, but do not rule out a role for calcium as a regulatory factor. 相似文献