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)

Injections of parathyroid hormone (PTH) result in increased bone formation in several species. Work in our laboratory and others has shown a stimulation of bone cell proliferation and growth factor production by PTH. Our purpose was to study the effects of PTH on a human bone cell line using TE-85 human osteosarcoma cells as a model. After 24 h treatment, PTH caused an increase in cell proliferation as measured by cell counts and [3H]-thymidine incorporation. Proliferation was not inhibited by an anti-transforming growth factor beta (TGF beta) antibody which could abolish stimulation by exogenous TGF beta. PTH did not stimulate cAMP production, alkaline phosphatase activity or production of insulin-like growth factors I or II (IGF-I or IGF-II) in TE-85 cells. Although basal TE-85 proliferation was slowed by incubation with the calcium channel blocking agent verapamil, PTH still caused an increase in growth rate. We conclude that PTH directly stimulates TE-85 proliferation via a mechanism not involving increased adenylate cyclase activity or increased secretion of IGF-I, IGF-II or TGF beta and may stimulate bone formation in vivo by activating some other mitogenic signal to increase bone cell proliferation.
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PMID:PTH stimulates the proliferation of TE-85 human osteosarcoma cells by a mechanism not involving either increased cAMP or increased secretion of IGF-I, IGF-II or TGF beta. 131 2

Calcium channel blockers have been reported to have such diverse effects on reduction in protein synthesis, diminished incorporation of proline into new collagen, and decreased hormone release in vitro. The chronic affect of the calcium channel blocker nifedipine was examined in vivo to determine the possible impact of pharmacologic calcium channel blockade on bone metabolism. Eleven Caucasian males treated with an average of 40 mg/d nifedipine for an average of three years were compared to 11 control males matched for age, height, weight, activity level, cardiovascular status, and calcium intake. No significant differences between groups were noted in bone mineral density at the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle and trochanter), and proximal and distal radius. There were also no significant differences in parameters of bone turnover (alkaline phosphatase, osteocalcin, urine calcium/creatinine, and hydroxyproline/creatinine ratio), or hormones that might affect calcium metabolism and bone (testosterone, PTH, 25(OH) vitamin D, and calcitonin). In summary, chronic nifedipine use in males is not associated with either a beneficial or adverse effect on bone metabolism.
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PMID:Chronic use of the calcium channel blocker nifedipine has no significant effect on bone metabolism in men. 205 35

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

The effect of sodium fluoride on alkaline phosphatase (ALP) release and [3H]thymidine uptake by human osteoblasts in culture was investigated. Sodium fluoride stimulated both ALP release and [3H]thymidine uptake at concentrations of sodium fluoride greater than 250 mumol/L. This stimulation was similar in magnitude to that induced by 1,25-dihydroxycholecalciferol. The fluoride-induced increase in ALP was inhibited by verapamil, a calcium channel blocker. We conclude that sodium fluoride stimulates osteoblasts to proliferate and to release ALP. This stimulation by fluoride is dependent on calcium influx. Fluoride-induced stimulation of human osteoblasts may be relevant to its effect in enhancing bone formation in patients with osteoporosis.
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PMID:Fluoride stimulates [3H]thymidine incorporation and alkaline phosphatase production by human osteoblasts. 223 70

We have investigated the actions of human PTH [hPTH-(1-34)] on the association of 45Ca2+ with two human (SaOS-2 and MG-63) and two rat (ROS 17/2.8 and UMR-106) osteoblast-like cell types. In SaOS-2 cells, hPTH-(1-34) binds to specific membrane receptors to activate adenylate cyclase. Treatment of SaOS-2 cells with hPTH-(1-34) resulted in an increase in 45Ca2+ uptake, in a dose-dependent fashion, up to 2- to 4-fold above control values. The increase was first evident at 10 min and persisted for at least 30 min. Treatment with nimodipine, a calcium channel antagonist, was without effect on the stimulatory action of PTH. A similar enhancement of cell-associated 45Ca2+ was observed when the cells were incubated with vasoactive intestinal peptide, which acts via different receptors to activate adenylate cyclase in SaOS-2 cells. Treatment with (Bu)2cAMP also induced an increase in cell-associated 45Ca2+. Pretreatment of SaOS-2 cells with hPTH-(1-34) for 4 h, which induced homologous desensitization to a second challenge with the same peptide for stimulation of cAMP production, did not attenuate the further enhancement of cell-associated 45Ca2+ by a second treatment with hPTH-(1-34). We then examined a possible relationship between alkaline phosphatase (ALPase) and 45Ca2+ uptake. SaOS-2 cells contained high levels of alkaline phosphatase activity and continuously released the enzyme into the medium. Release was enhanced by treatment with hPTH-(1-34) for 10 min. Incubation of cells with levamisole (an inhibitor of the liver/bone/kidney type of ALPase) resulted in a rapid decrease in basal and PTH-stimulated 45Ca2+ uptake, while treatment with L-Phe-Gly-Gly (an inhibitor of human placental ALPase) was without effect. Treatment of the cells with ALPase (bovine kidney) enhanced 45Ca2+ uptake. In MG-63 cells, a stimulatory effect of hPTH-(1-34) on cell-associated 45Ca2+ was also observed; however, hPTH-(1-34) did not stimulate cAMP production in MG-63 cells. In ROS 17/2.8 cells, neither hPTH-(1-34) nor rat PTH-(1-34) stimulated an increase in cell-associated 45Ca2+, while in UMR-106 cells, rat PTH-(1-34) and (Bu)2cAMP did enhance 45Ca2+ uptake, although hPTH-(1-34) was without effect. We conclude that PTH can stimulate an increase in cell-associated 45Ca2+ in several osteoblast-like cell lines, possibly by modulating local ALPase activity; however, this action of PTH does not appear to be obligatorily dependent on the adenylate cyclase-stimulating action of PTH.
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PMID:Stimulation by parathyroid hormone of 45Ca2+ uptake in osteoblast-like cells: possible involvement of alkaline phosphatase. 231 51

The mechanism of calmodulin-stimulated alkaline phosphatase activity was studied in the rat. In calmodulin-treated rats (2.5 micrograms/animal, intraperitoneally) alkaline phosphatase (ALP) activity was elevated 11-fold in the ileum, 1.5-fold in the duodenum and calvarium, 3-fold in serum, and not at all in liver. The elevated ALP activity was prevented by prior treatment with flunarizine, a calcium channel blocker, and by W-7, a calmodulin antagonist. cAMP content in ileum paralleled the timing and changes in ALP activity, but was not elevated in the duodenum or calvarium. Calcium ionophore A23187 and calcitonin treatment also increased ileal, duodenal, and calvarial ALP activity, but by less than the response to calmodulin. All of these treatments caused a 2-fold elevation in serum 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3) levels. Pretreatment of the animals with parathyroid hormone prevented the rise of both ALP activity and of 1,25(OH)2D3. Administration of 1,25(OH)2D3 alone stimulated a different pattern of increased ALP activity, greater in duodenum than ileum. The uptake of 45Ca by calmodulin was also elevated in ileum and calvarium. These data suggest that shifts in calcium movement, perhaps mediated by vitamin D, can alter ALP activity, and may provide a mechanism for rapid control of the secretion of this enzyme.
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PMID:Rat ileal alkaline phosphatase activity and secretion is stimulated by alterations in calcium metabolism. 253 9

Subchronic oral exposure of dogs to Oxodipine, a new calcium channel blocker of the dihydropyridine-type, resulted in dose-related gingival hyperplastic changes. The doses at which an effect was elicited were 24 and 73 times the intended therapeutic dose for man. The effects were first noted after 7 weeks of treatment, and were limited to the high and intermediate dose groups of both sexes. Macroscopically, a generalized enlargement of the maxillary and mandibular facial and lingual gingivae were noted. The histological changes were similar to those described in man for Nifedipine and hydantoin-related drugs. An increase in the activity of alkaline phosphatase and a decrease in alanine aminotransferase was demonstrated. This article is the first to describe gingival hyperplasia in dogs induced in a dose-dependent manner by a calcium channel blocker.
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PMID:Gingival hyperplasia in dogs induced by oxodipine, a calcium channel blocking agent. 319 54

The effect of exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3 on small-intestinal calcium and glucose transport in the rat was studied at the level of brush-border membrane vesicles generated from isolated villous cells by a freeze-thaw procedure. At 5 X 10(-5) M extravesicular calcium, initial uptake rates in vesicles prepared from triamcinolone-treated adult rats were decreased by 30% after 5 days. Since calcium ionophore A23187 virtually abolished the difference in calcium uptake, triamcinolone appeared to affect calcium channel density or activity rather than intravesicular binding capacity. Kinetic analysis showed that a decrease in Vmax of a saturable calcium transport system could entirely account for the diminished rate of vesicular calcium uptake. Calcium transport rates could be partially restored by in vivo administration of 1,25-dihydroxyvitamin D-3 at a dosage which did not affect vesicular calcium uptake in control animals. Conversely, sodium-driven glucose accumulation in brush-border vesicles from triamcinolone-treated rats was stimulated by 50-70% after 36 h and appeared insensitive to vitamin D. A specific triamcinolone action on the glucose carrier itself rather than on the driving force of the sodium gradient was indicated by (i) a similar stimulation of glucose transport under equilibrium exchange conditions and (ii) an opposite effect of triamcinolone on sodium-driven alanine transport. The triamcinolone-induced changes in calcium and glucose uptake were not accompanied by a gross alteration of membrane integrity in vitro or by major alterations in vesicular protein composition, intravesicular glucose space and sucrase or alkaline phosphatase activity. The modification of vesicular transport properties is discussed in relation to the vitamin D-antagonized inhibition of intestinal calcium uptake and the stimulation of glucose absorption in response to supraphysiologic amounts of glucocorticoids observed in intact epithelium.
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PMID:Calcium and glucose uptake in rat small intestinal brush-border membrane vesicles. Modulation by exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3. 654 50

Osteoclasts attach to mineralized surfaces and resorb bone matrix, releasing calcium into the area surrounding the osteoclast. The production of high levels of extracellular calcium increases intracellular calcium concentrations ([Ca2+]i), and bone resorption is decreased. To study this mechanism, the dihydropyridine-sensitive L-type calcium channel antagonists PN 200-110, (-)202-791, and nifedipine were studied for their effects on bone resorption using the disaggregated osteoclast pit assay. Changes in [Ca2+]i after treatment with these compounds were determined with the fluoroprobe fura2. In osteoclast-enriched cultures, significant decreases in bone resorption were noted in the presence of PN 200-110 and (-)202-791. The decrease in bone resorption correlated with an increase in [Ca2+]i. To determine whether the effects of these compounds on osteoclasts were mediated via osteoblasts, proliferation and differentiation of rat osteoblast-like cells (ROS 17/2.8) were examined after the addition of these agents. There were no changes in osteoblast proliferation or differentiation, as determined by [3H]thymidine incorporation and specific activity of alkaline phosphatase, after treatment with these compounds at concentrations that inhibited bone resorption in the disaggregated pit assay. This lack of effect of calcium channel antagonists on osteoblast growth and differentiation at concentrations used to inhibit osteoclast function suggests that the effects of PN 200-110 and (-)202-791 on the osteoclast are not mediated via the osteoblast. In addition, conditioned medium recovered from ROS 17/2.8 cultures treated with PN 200-110 or (-)202-791 had no effect on pit formation compared to the conditioned medium from cell-free cultures. This lack of effect of calcium channel conditioned medium on bone resorption provides additional evidence that PN 200-110 and (-)202-791 are decreasing bone resorption directly by altering osteoclast function, not through osteoblast-osteoclast interactions. The addition of (-)202-791 or PN 200-110 to osteoclasts resulted in a dose-dependent rise in [Ca2+]i. These data suggest that calcium channel antagonists may bind to the calcium channel of the osteoclast and lock it in an open state, leading to increased [Ca2+]i and decreased bone resorption.
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PMID:Direct effect of calcium channel antagonists on osteoclast function: alterations in bone resorption and intracellular calcium concentrations. 807 Mar 95

A prospective double-blind randomized cardioangiographic study with iopentol and iohexol was performed in 60 patients. Glomerular filtration rate (GFR) was assessed by serum values of creatinine and beta 2-microglobulin (beta 2-MG), estimated creatinine clearance (CCr) according to Cockroft & Gault's formula, and 24 hour CCr. The urinary excretion of albumin, beta 2-MG, and of the renal tubular enzymes alkaline phosphatase (ALP) and N-acetyl-beta-glucosaminidase (NAG) was also measured. Contrary to what has been found after i.v. injections, GFR was reduced by both nonionic contrast media. Serum creatinine (S-Cr) was increased by more than 25% in 6 patients, 3 in each group. CCr was more sensitive than S-Cr and S-beta 2-MG, but this method is less precise because of risk of urine sampling errors. Estimated CCr gave no additional information to S-Cr. The urinary excretion of NAG and ALP was increased. No clinically significant differences between iopentol and iohexol were detected. No correlation was found between the changes in tubular function parameters and changes in GFR. Twenty patients were on calcium channel blockers before the investigation, but this had no protective effect on the renal function parameters.
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PMID:Renal effects of nonionic contrast media after cardioangiography. 817 50


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