Carbon dioxide and the effect of parathyroid hormone on bone in vitro

Mahgoub, Amar; Stern, P.

doi:10.1152/ajplegacy.1974.226.6.1272

Cited by 25 publications

(12 citation statements)

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“…6). These levels compare favorably with concentrations of parathyroid hormone used in other studies on bone and kidney adenylyl cyclase activation that used levels of 10,000 and 85,000 ng/ml, respectively (39,37), and with other in vitro studies of parathyroid hormone action on kidney and bone metabolism (42,43). The quantities of parathyroid hormone producing significant metabolic effects in this study in vitro are approximately one to two orders of magnitude greater than circulating levels of parathyroid hormone in normal man (0.50 ng/ml; 44,45).…”

Section: Discussionsupporting

confidence: 55%

Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat

Garber¹

1983

J. Clin. Invest.

127

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A B S T R A C T Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 105 ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [3HJleucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-14C]arginine in vivo, parathyroid hormone increased the rate of loss of 14C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or

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Section: Discussionsupporting

confidence: 55%

Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat

Garber¹

1983

J. Clin. Invest.

127

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“…These findings led to our suggestion that skeletal carbonic anhy drase, reported to be in osteoclasts [4], might play a significant role in the mechanism of bone resorption [1], Others have made relevant contributions in this area. Acetazolamide, when added to bone cultures in vitro, inhibits PTH-induced bone resorption [5][6][7], an effect which has been recently confirmed in our laboratory [8]. Waite [9] has reported that inhibition of PTH-induced hypercalcemia in nephrectornized-parathyroidectomized rats is also seen with other carbonic anhydrase inhibitors (methazolamide and ethoxolamide).…”

Section: Introductionmentioning

confidence: 74%

Role of Carbonic Anhydrase in Bone: Plasma Acetazolamide Concentrations Associated with Inhibition of Bone Loss

Kenny¹

1985

Pharmacology

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Earlier reports from our laboratory have indicated that the carbonic anhydrase inhibitor acetazolamide blocks the hypercalcemic response to parathyroid hormone. In addition, we have reported that acetazolamide when administered by several routes partially prevents denervation-induced bone loss in a rat model of disuse osteoporosis. Continuous subcutaneous infusion required the least daily dose (8 mg/kg). The present study extends these earlier findings in several ways. It was found that in partially preventing denervation-induced bone loss: (1) incorporation of 1 M THAM [tris(hydroxymethyl)aminoethane] enhanced the potency of acetazolamide such that it was effective at daily doses of 0.6 mg/kg; (2) acetazolamide in the presence of 1 M THAM was effective at plasma concentrations as low as 50 ng/ml which are more than 500-fold less than peak plasma concentrations normally encountered in the human when acetazolamide is being used as a therapeutic agent; and (3) another inhibitor, benzolamide, was also effective by continuous subcutaneous infusion.

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“…Both in vivo and in vitro evidence from our laboratory [8][9][10][11][12][13] and from other labora tories [14][15][16][17][18][19][20] provided strong evidence for such a role for carbonic anhydrase. For ex ample, Kenny and co-workers showed that the carbonic anhydrase inhibitor acetazolam ide was effective in preventing PTH-induced hypercalcemia in parathyroidectomized- were cultured as described in figure 3.…”

Section: Discussionmentioning

confidence: 99%

“…Results from our laboratory [8][9][10][11][12][13] and other laboratories [14][15][16][17][18][19][20] have implicated the enzyme carbonic anhydrasc (EC 4.2.1.1), which is present in osteoclasts [21], as a nec essary component of the resorptive mecha nism. Recently, we have shown that both PTH-and l,25-(OH)2D3-enhanced bone re sorption is accompanied by 2-and 3-fold increases in skeletal carbonic anhydrasc activ ity [22,23].…”

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confidence: 99%

Role of Carbonic Anhydrase in Bone Resorption Induced by Prostaglandin E<sub>2</sub> vitro

Hall

Kenny

1985

Pharmacology

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The possible role of carbonic anhydrase in bone resorption induced by prostaglandin E₂ (PGE₂) was studied using an in vitro neonatal mouse calvarial culture system. PGE₂ (10^–6M) was effective in stimulating resorption, as assessed by calcium release into culture media. This enhanced resorption was accompanied by significant increases in calvarial carbonic anhydrase activity over control values at 48 and 96 h. At 48 h, bones treated with PGE₂ had 20% more carbonic anhydrase activity than controls. By 96 h, treated bones contained 79% more carbonic anhydrase activity than controls. PGE₂-induced bone resorption was inhibited by the carbonic anhydrase inhibitor acetazolamide in a dose-dependent fashion from 10^–5 to 10^–4M, with 77% inhibition observed at 10^–4M. The acetazolamide analogue CL 13,850 (N-t-butylacetazolamide), which does not inhibit carbonic anhydrase, failed to inhibit PGE₂-induced resorption. These results are consistent with the hypothesis that carbonic anhydrase is a necessary component of the osteoclastic bone resorptive mechanism.

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Carbon dioxide and the effect of parathyroid hormone on bone in vitro

Cited by 25 publications

References 0 publications

Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat

Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat

Role of Carbonic Anhydrase in Bone: Plasma Acetazolamide Concentrations Associated with Inhibition of Bone Loss

Role of Carbonic Anhydrase in Bone Resorption Induced by Prostaglandin E<sub>2</sub> vitro

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