1,25(OH)2D3 increases cytosolic Ca++ concentration of osteoblastic cells, clone MC3T3-E1

Oshima, Joji; Watanabe, Masahiro; Hirosumi, Jiro; Orimo, Hajime

doi:10.1016/0006-291x(87)91058-8

Cited by 31 publications

(13 citation statements)

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“…In addition to altering cellular calcium in osteoblasts, the hormone increases nuclear calcium [Sorensen et al, 1993a1, cellular calcium uptake [Kim et al, 1987Lieberherr, 1987;Oshima et al, 1987; Caffrey et al, 19891, phospholipase C activity [Civitelli et al, 1990; Grosse et al, 19931, and intracellular pH [Jenis et al, 19931. These nongenomic effects of la, 25-(OH)zD3 have a functional significance in osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D₃

Baran

1994

J of Cellular Biochemistry

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Recent studies indicate that the vitamin D hormone, 1 alpha,25-dihydroxyvitamin D3 exerts rapid effects (seconds to minutes) in a variety of cell types. These rapid nongenomic actions in osteoblasts include effects on membrane voltage-gated calcium channels, phospholipase C activity, and the sodium/hydrogen antiport. Since the rapid effects occur in osteoblasts that lack the nuclear vitamin D receptor, it is postulated that the nongenomic responses to the hormone reflect interaction with a separate, membrane localized signalling system. Preliminary studies demonstrate the presence of a receptor on the membranes of osteoblasts that lack the nuclear vitamin D receptor. This membrane receptor recognizes 1 alpha,25-dihydroxyvitamin D3 and its inaction 1 beta epimer, but not 25-hydroxyvitamin D3. These rapid nongenomic actions generated by interaction with the membrane receptor modulate the effects of the hormone on gene transcription. Thus, the rapid nongenomic pathway may play a regulatory function in modulating the genomic pathways affected by 1 alpha,25-dihydroxyvitamin D3.

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Section: Introductionmentioning

confidence: 99%

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D₃

Baran

1994

J of Cellular Biochemistry

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“…These effects were not particularly specific since both 24,25-dihydroxyvitamin D,, 100 pM-10 nM, and 25-hydroxyvitamin D,, 10 and 100 nM, increased intracellular calcium. The effects of 1 a,25-dihydroxyvitamin D, on mouse osteoblasts were also demonstrated by Oshima et al (13). These effects occur within seconds, at concentrations as low as 2 pM, and also appear to depend upon the presence of extracellular calcium.…”

Section: Rapid Actions Of La25=dihydroxyvitamin D On Osteoblastsmentioning

confidence: 66%

Rapid Actions of 1 -25-Dihydroxyvitamin D3 Physiologic Role

Baran

Sorensen

1994

Experimental Biology and Medicine

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The steroid hormone, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-[OH]2D3), has been shown to exert actions on cells within seconds. The rapidity of these effects has led to the speculation that they reflect nongenomic actions of the hormone which involve interaction with membrane receptors. Moreover, these rapid effects appear to modulate the actions of the hormone on gene transcription, suggesting that the physiologic role of the rapid actions may involve the regulation of hormone induced gene activation.

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“…Other rapid (significant within <30 min) actions of la,25-(OH)2D3 have been described, including effects on adenylate cyclase in the kidney (11) and parathyroid (27); on transmucosal calcium transport in duodenum (7,8,28,29); on cytosolic calcium in the liver (9), parathyroid (14), epidermis (13), and osteoblastic cells (12,30); on membrane potential in cartilage and renal proximal tubule (6); and on phospholipid metabolism in multiple tissues (5,31,32). The transduction mechanisms for these rapid actions of la,25-(OH)2D3 have not been established.…”

Section: Discussionmentioning

confidence: 99%

“…The most widely accepted explanation is that the rapid actions of steroids are receptor independent; direct action on the cell membrane modulates its lipid composition, changes ion fluxes, and activates ion-dependent metabolic processes (2)(3)(4). However, recent data indicate that rapid actions of la,25-(OH)2D3 can occur at very low concentrations (5)(6)(7)(8)(9)(10)(11)(12) and with high cholecalciferol analog specificity (6,7,(9)(10)(11)(12)(13)(14)(15), suggesting to us that the la,25-(OH)2D3 receptor could mediate rapid actions.…”

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confidence: 97%

Receptor-mediated rapid action of 1 alpha,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts.

Bársony

Marx

1988

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

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The intracellular cGMP concentration in normal human cultured fibroblasts was increased 2-to 3-fold by la,25-dihydroxycholecalciferol [la,2D3] in a dosedependent manner between 0.01 nM and 1 FM. The response was detectable within 1 min, reached a maximum (225% ± 8% of baseline) at 6-8 min, and was no longer detectable at 30 min. The half-maximal effect of la,25-(OH)2D3 was at 1.8 nM, and 24,25-dihydroxycholecalciferol showed an estimated ECso 100-fold higher. 113,25-Dihydroxycholecalciferol, 25-hydroxycholecalciferol, and cholecalciferol had no detectable effect. Human skin fibroblasts with three different types of la,25-(OH)2D3 receptor defect did not respond to la,25-(OH)2D3 exposure with cGMP increase; however, the same cells (like normal cells) responded to testosterone or sodium nitroprusside with a rapid rise of cGMP. We conclude that the rapid rise of cGMP in response to calciferols shows an ECse for la,25-(OH)2D3, a cholecalciferol analog specificity, and a cell line dependency that are all suggestive of mediation through a specific la,25-(OH)2D3 receptor.Over the past 15 years, studies from a number of laboratories have provided evidence that la,25-dihydroxycholecalciferol [la,25-(OH)2D3 or calcitriol] acts like a steroid hormone through receptor-mediated regulation of nuclear events. However, rapid, presumably nongenomic, actions of la,25-(OH)2D3 (similar to those of other steroid hormones) have been documented in several systems (1). The most widely accepted explanation is that the rapid actions of steroids are receptor independent; direct action on the cell membrane modulates its lipid composition, changes ion fluxes, and activates ion-dependent metabolic processes (2-4). However, recent data indicate that rapid actions of la,25-(OH)2D3 can occur at very low concentrations (5-12) and with high cholecalciferol analog specificity (6, 7, 9-15), suggesting to us that the la,25-(OH)2D3 receptor could mediate rapid actions.Rapid stimulation of cGMP by steroids (16-19) including la,25-(OH)2D3 (20) cinyl-cGMP-tyrosine methyl ester (specific activity, >2000 ,Ci/1 ,umol; 1 Ci = 37 GBq) was from Meloy Laboratories (Springfield, VA). Antiserum against cGMP (no. 33:5-6-81) was provided by Kevin Catt. All cholecalciferol analogs were tested for purity on reverse-phase high-performance liquid chromatography within a week before use (21).Cell Culture. All studies were performed on human cultured skin fibroblasts. Three cell lines from patients with hereditary resistance to la,25-(OH)2D3 had been tested previously for la,25-(OH)2D3 receptor binding, for la,25-(OH)2D3 nuclear uptake, and for la,25-(OH)2D3 receptor elution from DNA-cellulose to characterize their defects in la,25-(OH)2D3 action (21-23) ( and maintained for 24 hr in serum-free medium. Cell cultures from passages 12-30 were used at 75% confluency. Cells were tested for mycoplasma (American Type Culture Collection) with negative results.Perturbation of Intracellular cGMP. Immediately before exposure to hormones cells were washed three times wit...

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1,25(OH)2D3 increases cytosolic Ca++ concentration of osteoblastic cells, clone MC3T3-E1

Cited by 31 publications

References 16 publications

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D₃

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D₃

Rapid Actions of 1 -25-Dihydroxyvitamin D3 Physiologic Role

Receptor-mediated rapid action of 1 alpha,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts.

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1,25(OH)2D3 increases cytosolic Ca++ concentration of osteoblastic cells, clone MC3T3-E1

Cited by 31 publications

References 16 publications

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D3

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D3

Rapid Actions of 1 -25-Dihydroxyvitamin D3 Physiologic Role

Receptor-mediated rapid action of 1 alpha,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts.

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Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D₃

Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D₃