1,25-dihydroxyvitamin D-3 and 24,25-dihydroxyvitamin D-3 affect parathormone (PTH) - sensitive adenylate cyclase activity and alkaline phosphatase secretion of osteoblastic cells through different mechanisms of action

Klem, K H; Jablonski, Greg Eigner; Sæther, Olav; Jarosz, G.; Gautvik, Kaare M.; Gordeladze, Jan O.

doi:10.1016/0167-4889(90)90101-i

Cited by 14 publications

(3 citation statements)

References 31 publications

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“…Although it is claimed that a possible function as a phosphodiesterase for cartilage and bone alkaline phosphatases is unlikely in vivo [19], bone-metabolism studies show that increasing levels of cyclic AMP stimulate not only collagen synthesis but also alkaline phosphatase activity [20][21][22][23][24]. Furthermore, calmodulin, a known activator of cyclic nucleotide phosphodiesterases [25], was recently shown to activate chick alkaline phosphatase [26].…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase activity is a novel property of alkaline phosphatase from osseous plate

Rezende¹,

Pizauro²,

Ciancaglini³

et al. 1994

Biochemical Journal

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Phosphodiesterase activity is a novel property of the still-enigmatic alkaline phosphatase from osseous plate. Bis-(p-nitrophenyl) phosphate was hydrolysed at both pH 7.5 and 9.4 with an apparent dissociation constant (K0.5) of 1.9 mM and 3.9 mM respectively. The hydrolysis of p-nitrophenyl-5'-thymidine phosphate followed hyberbolic kinetics with a K0.5 of 500 microM. For p-nitrophenyl phenylphosphonate, site-site interactions [Hill coefficient (h) = 1.3] were observed in the range between 0.2 and 100 microM, and K0.5 was 32.8 mM. The hydrolysis of cyclic AMP by the enzyme followed more complex kinetics, showing site-site interactions (h = 1.7) and K0.5 = 300 microM for high-affinity sites. The low-affinity sites, representing 85% of total activity, also showed site-site interactions (h = 3.8) and a K0.5 of about 22 mM. ATP and cyclic AMP were competitive inhibitors of bis-(p-nitrophenyl) phosphatase activity of the enzyme and Ki values (25 mM and 0.6 mM for cyclic AMP and ATP respectively) very close to those of the K0.5 (22 mM and 0.7 mM for cyclic AMP and ATP respectively), determined by direct assay, indicated that a single catalytic site was responsible for the hydrolysis of both substrates. Non-denaturing PAGE of detergent-solubilized enzyme showed coincident bands on the gel for phosphomonohydrolase and phosphodiesterase activities. Additional evidence for a single catalytic site was the similar pKa values (8.5 and 9.7) found for the two ionizing groups participating in the hydrolysis of bis-(p-nitrophenyl) phosphate and p-nitrophenyl phosphate. The alkaline apparent pH optima, the requirement for bivalent metal ions and the inhibition by methylxanthines, amrinone and amiloride demonstrated that rat osseous-plate alkaline phosphatase was a type I phosphodiesterase. Considering that there is still confusion as to which is the physiological substrate for the enzyme, the present results describing a novel property for this enzyme could be of relevance in understanding the mineralization process.

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Section: Introductionmentioning

confidence: 99%

Phosphodiesterase activity is a novel property of alkaline phosphatase from osseous plate

Rezende¹,

Pizauro²,

Ciancaglini³

et al. 1994

Biochemical Journal

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“…Furthermore, calcitriol enhances PIP2 turnover in enterocytes and augments both PLC and PLA2 activities in parathyroid cells (107). Finally, (24R)-hydroxycalcidiol impedes Ca + fluxes in bone cells, and also appears to hamper specifically the PTH receptor Gs-protein coupling in osteoblasts (105,(108)(109)(110).…”

Section: Non-genomic Action Of Steroid Hormonesmentioning

confidence: 96%

“…the presence of specific G-proteins vary in the anterior pituitary during the oestrous cycle (93) and in the myometrium during gestation (172). To the non-genomic action of steroids belongs the effect of (24R)-hydroxycalcidiol, which has been shown to block acutely the effect of PTH on osteoblastic AC (108,109). The mechanism by which (24R)-hydroxycalcidiol exerts its effect may be by hampering the coupling between the PTH receptor and the Gs-protein (105,109).…”

Section: Mutations In Gsa and Gi2amentioning

confidence: 98%

G-Proteins: implications for pathophysiology and disease

Gordeladze

Johansen²,

Paulssen³

et al. 1994

European Journal of Endocrinology

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This article focuses on the involvement of G-proteins in neuroendocrine secretion, cell growth and phenotype alterations. The current concept of hormonal activation of the GTPase cycle, as well as the molecular diversity of G-proteins families and receptor*G-protein*effector coupling, are described. Also described are certain G-proteins as possible proto-oncogenes and how point mutations and frame shift mutations alter G-protein function and determine the characteristics of various endocrine diseases. The article outlines in detail how receptors and G-proteins interact in prolactin and growth-hormone-secreting pituicytes, how G-proteins are involved in the growth and differentiation of preadipocytes and osteoblasts. All in all, it seems that hormonal activation through G-proteins is modulated through direct intra- and inter-signalling system cross-talk at the plasma membrane level (short-term) and through interactions on the level of transcription (HREs) from tyrosine kinases, steroid-like hormones and metabolic pathways. Pharmacological intervention to treat diseases where G-proteins are involved should take both long and short-term regulatory phenomena into consideration.

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Activation of the human osteocalcin gene by 24r,25-dihydroxyvitamin d3 occurs through the vitamin d receptor and the vitamin d-responsive element

Uchida

Ozono

1994

Journal of Bone and Mineral Research

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1 alpha-25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], together with vitamin D receptor (VDR), directly activates human osteocalcin (hOC) gene expression through a vitamin D-responsive element (VDRE) located in the promoter of the hOC gene. We investigated the effect of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on the regulation of the hOC gene promoter and compared it with that of 1 alpha,25(OH)2D3. 24R,25(OH)2D3 did not activate the natural promoter in VDR-negative CV-1 cells. 24R,25(OH)2D3, however, induced the activation of this promoter following cotransfection with an hVDR expression vector. In VDR-positive MC3T3-E1 cells, 24R,25(OH)2D3 activated not only the natural hOC promoter but also a chimeric promoter composed of a synthetic hOC VDRE sequence linked to the thymidine kinase promoter. In combination with 1 alpha-25(OH)2D3, 24R,25(OH)2D3 did not exhibit any antagonist activity on the hOC promoter. These results suggest that under conditions of high 24R,25(OH)2D3 levels in vivo, this metabolite of vitamin D3 may activate hOC gene expression through receptor mechanisms identical to that for 1 alpha,25(OH)2D3.

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1,25-dihydroxyvitamin D-3 and 24,25-dihydroxyvitamin D-3 affect parathormone (PTH) - sensitive adenylate cyclase activity and alkaline phosphatase secretion of osteoblastic cells through different mechanisms of action

Cited by 14 publications

References 31 publications

Phosphodiesterase activity is a novel property of alkaline phosphatase from osseous plate

Phosphodiesterase activity is a novel property of alkaline phosphatase from osseous plate

G-Proteins: implications for pathophysiology and disease

Activation of the human osteocalcin gene by 24r,25-dihydroxyvitamin d3 occurs through the vitamin d receptor and the vitamin d-responsive element

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