Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbonic anhydrase localized in bone resorptive cells generates the protons necessary for bone resorption. Inhibition of the enzyme is a potential mechanism for decreasing bone resorption. Eight healthy post-menopausal women received oral acetazolamide 250 mg twice daily for 28 d. Bone resorption, evaluated by serum acid phosphatase activity and the renal excretion of hydroxyproline, was unaltered, as was bone formation estimated by serum levels of alkaline phosphatase and osteocalcin. The fasting renal excretion of calcium was increased, whereas serum ionized calcium was unchanged. The maximal renal reabsorption of phosphate decreased, but it was not an effect of PTH as it decreased significantly during the treatment period. In conclusion, no significant effect on biochemical markers of bone remodelling could be detected during the study period. The observed changes in calcium and phosphate metabolism may be secondary to the renal effect of acetazolamide.
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PMID:The effect of carbonic anhydrase inhibition on calcium and bone homeostasis in healthy postmenopausal women. 212 65

We report serum 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in untreated Paget's disease and the effect of treatment with either calcitonin (CT) or etidronate (EHDP) on these levels. In untreated Paget's patients serum 25-OHD (73 +/- 29 nmol/liter, n = 36, mean +/- SD) and 24,25-(OH)2D (0.3-12.9 nmol/liter, median 2.2, n = 36) levels were significantly lower than in age-matched controls (94 +/- 30 nmol/liter, n = 32, p less than 0.005, and 1.3-16.4 nmol/liter, median 5.3; n = 32, p less than 0.001, respectively). Also, the 24,25-(OH)2D levels correlated with the 25-OHD levels in the untreated Paget's patients (r = 0.56, p less than 0.01) and in the controls (r = 0.39, p less than 0.05). The percentage molar ratio of 24,25-(OH)2D to 25-OHD in Paget's patients had a median value of 3.7% (range 0.4-14.3%), which was not significantly different from controls, who had a median value of 5.6% (range 2.2-18%). There was no difference between the 1,25-(OH)2D, and immunoreactive PTH (iPTH) levels of Paget's patients and control subjects. The percentage molar ratio of 1,25-(OH)2D to 25-OHD in untreated Paget's patients (0.157 +/- 0.09%) was not significantly different from controls (0.124 +/- 0.05%) despite lower 25-OHD levels in Paget's patients. There was a significant inverse correlation between the severity of Paget's disease as measured by plasma alkaline phosphatase (AP) levels and 25-OHD levels (r = 0.392, p less than 0.02); however, 24,25-(OH)2D and 1,25-(OH)2D levels were not correlated with AP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in vitamin D metabolites during treatment of Paget's disease of bone with calcitonin or etidronate. 212 1

We treated nineteen haemodialysis patients with secondary hyperparathyroidism with increasing oral doses of 1,25 dihydroxycholecalciferol (calcitriol) over a 12-week period and used low calcium dialysate (1.0 mmol/l) to prevent hypercalcaemia. Nine patients received daily calcitriol and ten received calcitriol thrice weekly, and at the end of the study the mean doses were 2.0 micrograms daily and 2.6 micrograms thrice weekly respectively. The regimen was well tolerated with nine episodes of mild hypercalcaemia, none of which were symptomatic. Mean PTH and alkaline phosphatase concentrations decreased from 62.0 pmol/l (15-125) to 22.0 pmol/l(1-70) (P less than 0.01), and 144 IU/l (48-461) to 123 IU/l (61-346) (P less than 0.05) respectively. Mean serum calcium increased from 2.33 mmol/l (2.05-2.55) to 2.52 mmol/l (2.26-2.67) (P less than 0.01). There were no significant changes in serum phosphate, magnesium, or aluminium concentrations and there were no significant differences in outcome between patients receiving daily therapy compared to those receiving it thrice weekly. A combination of high-dose oral calcitriol and low calcium dialysate can reverse secondary hyperparathyroidism without causing hypercalcaemia and these results suggest a benefit over conventional low-dose calcitriol.
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PMID:Low calcium dialysate and high-dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients. 212 83

Estrogen deficiency results in bone mass reduction of largely varying extent in postmenopausal females, indicating that additional mechanisms influence the response of bone. They are by no ways identified in either the animal experiment or under clinical conditions. In search for factors, conditioning the response of bone to estrogen deficiency, we have conducted a study in females under treatment with the GnRH agonist decapeptyl (D-Trp6-LHRH). This drug blocks ovarian function and was administered for treatment of endometriosis or uterine leiomyoma. We determined spinal (dual photon absorptiometry) and forearm (single photon absorptiometry) bone mineral density before and 3 and 6 months after the onset of therapy and measured biochemical parameters of bone metabolism. Our results showed an increase in bone turnover after initiation of estrogen deficiency, as indicated by the elevation of alkaline phosphatase and osteocalcin. This resulted in a secondary decrease in serum intact PTH and 1,25-dihydroxy-vitamin D3. Furthermore, we found a positive correlation between pretreatment values of serum 1,25-dihydroxyvitamin D3 as well as its decrease and the reduction in bone mass during GnRH agonist treatment. This demonstrates that the patients' metabolic conditions predict their response to estrogen deficiency.
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PMID:Bone mass reduction after estrogen deprivation by long-acting gonadotropin-releasing hormone agonists and its relation to pretreatment serum concentrations of 1,25-dihydroxyvitamin D3. 213 29

The effect of long-acting medroxyprogesterone acetate (MPA) on the trabecular bone density in patients with glucocorticoid-induced osteoporosis (GCO) was evaluated. Thirteen steroid-dependent asthmatic male patients with GCO were administered 200 mg MPA intramuscularly at 6-week intervals and 1 g of elemental calcium daily for a period of 1 year. Ten additional matched steroid-dependent asthmatic male patients received 1 g of elemental calcium daily (controls). All 23 patients involved in the study had vertebral trabecular bone densitometry (TBD) by quantitative computed tomography (QCT) at baseline and at 6 and 12 months into the study. A 17% increase in TBD was found in the MPA-treated patients at 1 year (from 68.5 +/- 5 to 80.2 +/- 4 mg K2HPO4/cc) in contrast to the control group who experienced a 21% decrease in TBD during the same period of time (from 80.5 +/- 7 to 63.7 +/- 8 mg K2HPO4/cc) (T = 6.90, P = 0.0001 df = 21). There were no significant changes in other parameters followed during the study in the MPA-treated group (serum calcium, phosphorus, magnesium, PTH, alkaline phosphatase, triglycerides, total and HDL cholesterol, urinary excretion of calcium, phosphate, creatinine) except for a decrease in the serum luteinizing hormone (LH) and testosterone (P less than 0.01) as well as of the hydroxyproline-creatinine ratio (P less than 0.01). The results lend support to the hypothesis of a progesterone-glucocorticoid competitive antagonism at the bone level, though other possibilities can be entertained, and suggest MPA as an effective therapy for glucocorticoid-induced osteoporosis in men.
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PMID:Effective therapy of glucocorticoid-induced osteoporosis with medroxyprogesterone acetate. 214 69

Cells were isolated by sequential collagenase digestion from the parietal segments of one day old mice (Swiss albino BNL strain) and characterized for osteoblast parameters by alkaline phosphatase histochemistry and bovine parathyroid hormone (bPTH-(1-34] induced cAMP activity (protein binding assay). Phenytoin (DPH) reduced PTH stimulated cAMP activity nearly 3-fold in the presence and nearly 1.5-fold in the absence of added calcium. In the absence of PTH, DPH exerted no significant effect. Bay-K-8644, a calcium channel activator, appeared to approximate the PTH stimulation of cAMP activity, even in the presence of DPH. This study demonstrates that DPH has a direct effect on PTH stimulated cAMP activity in cultured murine osteoblasts.
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PMID:The effect of phenytoin on parathyroid hormone stimulated cAMP activity in cultured murine osteoblasts. 215 57

Chondrocytes of the growth plate are differentiating cells. Their evolution leads to matrix vesicle formation and to cartilage mineralization. This is an in vitro study of the plasma membrane of chondrocytes at two differentiation stages. Differences in protein and glycoprotein components, increased membrane fluidity, and responsiveness to PTH indicate that hypertrophic ("ossifying") chondrocytes possess a plasma membrane widely different from that of resting chondrocytes. Their plasma membrane is particularly enriched in alkaline phosphatase (Mr 70K). Purified matrix vesicles contain the 70K form of alkaline phosphatase, but a 50K species is also detectable, a signal of degradative process. In fact, proteins and glycoproteins of matrix vesicles are less numerous than those of cell plasma membranes. It is suggested that, in vivo, matrix vesicle formation may be mediated by Ca2(+)-activated neutral proteases.
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PMID:Modification of plasma membrane of differentiating preosseous chondrocytes: evidence for a degradative process in the mechanism of matrix vesicle formation. 215 2

We examined the possibility that periodontal ligament (PDL) cells can differentiate into osteoblasts and/or cementoblasts in freshly isolated PDL tissues and in cultured cells derived from PDL. PDL tissues were obtained from the incisor teeth of bovine lower jaws; gingival connective tissues of the same animals were used as controls. Freshly isolated PDL tissues and cultured PDL cells showed an intense alkaline phosphatase (ALPase) activity both histochemically and biochemically. The production of 3',5'-cyclic adenosine monophosphate (cAMP) was greatly increased in response to human parathyroid hormone [PTH(1-34)], in both freshly isolated PDL tissues and cultured PDL cells. In contrast, neither ALPase activity nor PTH-dependent cAMP production was detected in gingival connective tissues and cultured gingival fibroblasts. Furthermore, cultured PDL cells synthesized a protein immunologically cross-reactive with bovine bone gla protein (BGP), a highly reliable marker of osteoblastic cells. When 10(-8) M 1a, 25-dihydroxyvitamin D3 [1a,25(OH)2D3] was added to the PDL cell cultures, the synthesis of the BGP-like protein was increased 2- to 3-fold. The maximal level of the synthesis was obtained 72 h after the addition of 1a,25(OH)2D3. Gingival fibroblasts cultured with or without 1a,25(OH)2D3 did not produce any appreciable amounts of the BGP-like protein. These results indicate that the PDL cells have phenotypes typical of osteoblasts, indicating that they may differentiate into osteoblasts and/or cementoblasts.
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PMID:Fibroblastic cells derived from bovine periodontal ligaments have the phenotypes of osteoblasts. 216 45

In UMR 106 rat osteosarcoma cells, parathormone (1-34hPTH) and calcitonin (sCT) stimulated adenylate cyclase (AC) activity 5.5-and 2.8-fold, respectively. AC in osteoblasts (OB) from collagenase-treated calvaria of 3-day-old rats responded similarly to 1-34hPTH. In contrast, fibroblasts (mouse fibroblastomas) displayed a marginal 1-34hPTH sensitive AC. Osteoclasts (OC) of collagenase-treated rat calvariae, rat monocytes and mouse macrophages did not demonstrate 1-34hPTH inducable AC activity. Physiological concentrations of 24,25-dihydroxyvitamin D-3 attenuated PTH-sensitive AC in OB and UMR 106 cells within 20 min, while 1,25-dihydroxyvitamin D-3 showed no such immediate effect. In contrast, the AC response to Gpp(NH)p was unaffected by 24,25-(OH)2D3, indicating that 24,25-(OH)2D3 interrupts the coupling of the PTH receptor to the GTP binding protein Gs. OB and UMR 106 cells were also subjected to long-term (48 h) incubation with vitamin D-3 metabolites, 1-34hPTH or 20% serum from patients with secondary hyperparathyroidism (sHBT-serum), respectively. PTH-sensitive AC was markedly attenuated by pre-exposure to both 1-34hPTH and 1,25-(OH)2D3, while minimally affected by corresponding 24,25-(OH)2D3 and 20% sHPT-serum treatment. The secretion of alkaline phosphatase (Alphos) from the two cell types was strongly increased by 1-34hPTH, the effect being abolished by the presence of 24,25-(OH)2D3. Iliac crest biopsies of normal individuals exhibited a clear negative correlation between PTH-sensitive AC and corresponding serum 24,25-(OH)2D3 levels. Basal AC activity was, however, negatively correlated to serum 1,25-(OH)2D3 concentrations. In summary, the results show that 24,25-(OH)2D3 reduces PTH-stimulated AC activity in and Alphos secretion from osteoblastic bone cells by rapidly and directly interfering with the plasma membrane. These data reinforce the probable in vivo significance of 24,25-(OH)2D3. Moreover, the negative correlation between basal AC activity and serum 1,25-(OH)2D3 levels indicates a possible role for 1,25-(OH)2D3 in regulating bone cell synthesis of AC components in vivo.
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PMID: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. 216 95

Bone cells derived from human trabecular explants display osteoblastic features. We examined the modulation of alkaline phosphatase activity and cAMP production as the result of exposing trabecular explants to physiologic concentrations of dexamethasone for 4 weeks during cellular outgrowth and subculture. Cells treated with dexamethasone were observed to grow generally more slowly than control cells. Cells appeared larger and more polygonal, and staining for alkaline phosphatase was more intense in the dexamethasone-exposed cultures. There was a progressive increase in cellular PTH responsiveness with increasing duration of exposure of cells to dexamethasone. Cells grown for 6 weeks in 3 x 10(-8) M dexamethasone had a 10-fold increase in PTH-stimulated cyclic AMP accumulation. Dexamethasone-treated cells also had a significantly increased alkaline phosphatase activity. 1,25-(OH)2D3-stimulated alkaline phosphatase activity was increased approximately 20-fold. cAMP responses were significantly increased to PTH (21.7-fold), PGE1 (2.67-fold), and forskolin (4.81-fold), but not to cholera toxin. Dexamethasone-treated cells also had a mean decrease in 1,25-(OH)2D3-stimulated osteocalcin production to 26.2% of control values (p less than 0.001). Hydrocortisone treatment gave rise to similar effects but of smaller magnitude than those of dexamethasone. Testosterone did not have a significant effect on alkaline phosphatase activity or cAMP production. Skin fibroblasts showed a significant enhancement of alkaline phosphatase activity in response to dexamethasone, but of a much smaller magnitude than in bone cells. The phenotypic changes induced by long-term culture in dexamethasone are consistent with the promotion of a more differentiated osteoblastic phenotype.
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PMID:Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells. 217 56


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