Summary
Intravenous injection of chicks with bovine parathyroid hormone (1–34) (3.3 μg/100 g body wt.) or 16,16-dimethyl PGE2 (5 μg/100 g body wt.) caused rapid (3 minute) net inhibition of45Ca uptake into femur and calvarium. These agents also elevated bone adenosine 3′,5′-cyclic monophosphate (cAMP) but not guanosine 3′,5′-cyclic monophosphate (cGMP) levels at this time. Methylxanthine phosphodiesterase inhibitors (MXPI), caffeine, theophylline, and 3-isobutyl-1-methylxanthine (IBMX) (0.3–5 mg/100 g body wt.) similarly inhibited net45Ca uptake into femur and to a lesser extent calvarium. Plasma45Ca and total Ca levels were unaltered or showed a slight tendency to be increased over control values 3 minutes after injection. However, the effects of the non-MXPI, dibutyryl-cAMP (0.5–5 mg/100 g body wt.) on bone45Ca uptake were negligible. Of the MXPI, only IBMX elevated total cAMP levels in chick bone at 3 minutes. These data implicate but do not confirm a mediatory role for cAMP in the rapid inhibitory actions of PTH and PGEs on bone net45Ca uptake in chicks.
Similar content being viewed by others
References
Shaw AJ, Dacke CG (1985) Evidence for a novel inhibition of calcium uptake into chick bone in response to bovine parathyroid hormone (1–34) or 16,16-dimethyl PGE2 in vivo. J Endocrinol 105:R5-R8
Dacke CG, Shaw AJ (1987) Studies of the rapid effects of parathyroid hormone and prostaglandins on45Ca uptake into chick and rat bone in vivo. J Endocrinol 115:369–377
Kenny AD, Dacke CG (1974) The hypercalcaemic response to parathyroid hormone in Japanese quail. Endocrinology 61:15–23
Kirby GC, Dacke CG (1983) Hypercalcaemic responses to 16,16-dimethyl prostaglandin E2, a stable prostaglandin E2 analogue in chicks. J Endocrinol 99:115–122
Shaw AJ, Dacke CG (1986) A comparison of the effects of bovine parathyroid hormone 1–34 and methylated prostaglandin E2 analogues on plasma calcium and inorganic phosphate levels in immature chickens and rats. Gen Comp Endocrinol 61:164–172
Peck WA, Klahr S (1979) Cyclic nucleotides in bone and mineral metabolism. In: Greengard P, Robison GA (eds) Advances in cyclic nucleotide research, vol 11. Raven Press, New York, pp 89–130
Walling MW, Marvaso V, Bernard GW (1978) Stimulation of guanylate cyclase activity in cultured osteogenic murine calvarial mesenchymal cells by PTH, calcitonin and insulin. Biochem Biophys Res Comm 83:521–527
Vaes G (1968) Parathyroid hormone-like action of N6-2′-O-dibutyryl adenosine-3′-5′ (cyclic)-monophosphate on bone explants in tissue culture. Nature 219:939–940
Wells H, Lloyd W (1969) Hypercalcaemic and hypophosphatemic effects of dibutyryl cyclic AMP in rats after parathyroidectomy. Endocrinol 83:861–867
Ivey JL, Wright DR, Tashjian AH (1976) Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A. J Clin Invest 58:1327–1338
Tashjian AH, Ivey JL (1981) Stimulation of bone resorption in organ culture by cholera toxin. Biochem Biophys Res Comm 102:1055–1064
Lerner U, Gustafson GT (1979) Inhibitory effect of dibutyryl cyclic AMP on the release of calcium, inorganic phosphate and lysosomal enzymes from calvarial bones cultured for 24 hours. Acta Endocrinol 91:730–742
Lerner U (1980), Inhibition of bone resorption and lysosomal enzyme release from calvarial bones cultured for 24 hours: synergism between cyclic AMP analogues and phosphodiesterase inhibitors. Acta Endocrinol 94:138–144
Miyamoto E, Kuo JF, Greengard P (1969) Cyclic nucleotide-dependent protein kinases III. Purification and properties of adenosine 3′, 5′-monophosphate-dependent protein kinase from bovine brain. J Biol Chem 244:6395–6402
Drummond GI, Powell CA (1970) Analogues of adenosine 3′, 5′-cyclic phosphate as activators of phosphorylase to kinase and as substrates for cyclic 3′,4′-nucleotide phosphodiesterase. Mol Pharmacol 6:24–29
Heersche JNM, Fedak SA, Aurback GD (1971) The mode of action of dibutyryl adenosine 3′, 5′-monophosphate on bone tissue in vitro. J Biol Chem, 246:6770–6775
Shaw AJ, Dacke CG (1987) Effect of phosphodiesterase inhibitors on45Ca uptake into chick bone in vivo: further evidence for a cAMP role in the rapid responses to parathyroid hormone and prostaglandins. J Endocrinol 112(suppl):100
Atkins D, Hunt NN, Ingleton PM, Martin TJ (1977) Rat osteogenic sarcoma cells: isolation and effects of hormones on the production of cyclic AMP and cyclic GMP. Endocrinol 101:555–561
Fletcher AE, Allan EH, Casley DJ, Martin TJ (1986) Atrial natriuretic factor receptors and stimulation of cyclic GMP formation in normal and malignant osteoblasts. FEBS Lett 208:263–268
Partridge NC, Kemp BE, Veroni MC, Martin TJ (1981) Activation of adenosine 3′, 5′-monophosphate-dependent protein kinase in normal and malignant bone cells by parathyroid hormone, prostaglandin E2 and prostacyclin. Endocrinol 108:220–225
Liversey SA, Kemp BE, Re CA, Partridge NC, Martin TJ (1983), Selective hormonal activation of cyclic AMP-dependent protein kinase isoenzymes in normal and malignant osteoblasts. J Biol Chem 257:14983–14987
Rubin CS, Rangel-Aldao R, Sarkar D, Erlichman J, Fleischer N (1979) Characterisation and comparison of membrane-associated and cytosolic cAMP-dependent protein kinase. J Biol Chem 254:3797–3805
Beavo JA, Rogers NL, Crofford OB, Hardman JG, Sutherland EW, Newman EV (1970) Effect of xanthine derivatives on lipolysis and on adenosine 3′, 5′-monophosphate phosphodiesterase activity. Mol Pharmacol 6:597–603
Shaw AJ (1987) Studies on the effects of parathyroid hormone and prostaglandins on bone and calcium metabolism in chicks and immature rats in vivo. PhD Thesis, University of Aberdeen
Marcus R, Orner FB (1980) Parathyroid hormone as a calcium ionophore in bone cells: tests of specificity. Calcif Tissue Int 32:207–211
Rasmussen H (1970) Cell communication, calcium ion and cyclic adenosine monophosphate. Science 170:404–412
Dunlop M, Larkins RG, Court JM (1981) Methylxanthine effects on cyclic adenosine 3′, 5′-monophosphate phosphodiesterase activity in preparations of neonatal rat cerebellum: modification by trifluoperazine. Biochem Biophys Res Comm 98:850–857
Cheun WY (1980) Calmodulin plays a pivotal role in cellular regulation. Science 207:19–27
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shaw, A.J., Dacke, C.G. Cyclic nucleotides and the rapid inhibitions of bone45Ca uptake in response to bovine parathyroid hormone and 16,16-dimethyl prostaglandin E2 in chicks. Calcif Tissue Int 44, 209–213 (1989). https://doi.org/10.1007/BF02556566
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02556566