Summary
Rapidin vivo effects of 1,25-dihydroxyvitamin D3 on muscle calcium metabolism have been reported.In vitro studies have shown that exposure of vitamin D-deficient chick soleus muscles to the sterol for 1–10 minutes causes a significant stimulation of tissue45Ca uptake which can be suppressed by Ca channel blockers. A parallel increase in muscle membrane calmodulin content that could be mimicked by forskolin was observed. Experiments were carried out to obtain information about the mechanism underlying the fast action of 1,25-dihydroxyvitamin D3. Like the sterol, forskolin (10 μm) rapidly increased (+48% at 5 min) soleus muscle45Ca uptake and its effect could be reversed by nifedipine (50 μm). In agreement with these observations, 1,25-dihydroxyvitamin D3 markedly elevated tissue cAMP levels within 45 seconds to 5 minutes of treatment in a dose-dependent manner (10−11–10−7M). Moreover, incubation of isolated muscle microsomes with 1,25-dihydroxyvitamin D3 increased adenylate cyclase activity and caused a similar profile of stimulation of protein phosphorylation with [γ-32P]-ATP as forskolin. Major changes were detected in proteins whose calmodulin binding ability has been previously shown to be increased by 1,25-dihydroxyvitamin D3. In addition, the calmodulin antagonists fluphenazine and compound 48/80 abolished the increase in muscle Ca uptake and membrane calmodulin content produced by the sterol. The results suggest that 1,25-dihydroxyvitamin D3 activates muscle Ca channels through a direct membrane action which involves cAMP-dependent protein phosphorylation and calmodulin binding.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Curry OB, Basten JF, Francis MJO, Smith R (1974) Calcium uptake by sarcoplasmic reticulum of muscle from vitamin D-deficient rabbits. Nature 249:83–87
Matthews C, Heimberg KW, Ritz E, Agostini B, Fritzche J, Hasselbach W (1977) Effect of 1,25-dihydroxycholecalciferol on impaired calcium transport by the sarcoplasmic reticulum in experimental uremia. Kidney Int 11:227–235
de Boland AR, Gallego S, Boland R (1983) Effects of vitamin D3 on phosphate and calcium transport across and composition of skeletal muscle plasma cell membranes. Biochim Biophys Acta 733:264–270
Giuliani D, Boland R (1984) Effects of vitamin D3 metabolites on calcium fluxes in intact chicken skeletal muscle and myoblasts cultured in vitro. Calcif Tissue Int 36:200–205
de Boland AR, Boland R (1985) In vitro cellular muscle calcium metabolism. Characterization of effects of 1,25-dihydroxy-vitamin D3 and 25-hydroxyvitamin D3. Z Naturforsch [C] 40:102–108
de Boland AR, Boland R (1985) Suppression of 1,25-dihydroxy-vitamin D3-dependent calcium transport by protein synthesis inhibitors and changes in phospholipids in skeletal muscle. Biochim Biophys Acta 845:237–241
Simpson RU, Thomas GA, Arnold AJ (1985) Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem 260:8882–8891
Boland R, Norman A, Ritz E, Hasselbach W (1985) Presence of a 1,25-dihydroxy-vitamin D3 receptor in chick skeletal muscle myoblasts. Biochem Biophys Res Commun 128:305–311
Costa EM, Blau HM, Feldman D (1986) 1,25-Dihydroxyvitamin D3 receptors and hormonal responses in cloned human skeletal muscle cells. Endocrinology 119: 2214–2220
de Boland AR, Boland R (1987) Rapid changes in skeletal muscle calcium uptake induced in vitro by 1,25-dihydroxy-vitamin D3 are suppressed by calcium channel blockers. Endocrinology 120:1858–1864
de Boland AR, Massheimer V, Fernandez LM (1988) 1,25-Dihydroxyvitamin D3 affects calmodulin distribution among subcellular fractions of skeletal muscle. Calcif Tissue Int 43:370–375
Bauman VK, Valinietse MY, Babarykin DA (1984) Vitamin D3 and 1,25-dihydroxyvitamin D3 stimulate the skeletal muscle-calcium mobilization in rachitic chicks. Arch Biochem Biophys 231:211–216
Fernandez L, Massheimer V, de Boland AR (1988) Dihydroxy-vitamin D3 increases calmodulin binding to skeletal muscle membranes. In: Norman AW, Schaefer K, Grigoleit HG, Herrath DV (eds) Vitamin D, molecular, cellular and clinical endocrinology. Walter de Gruyter & Co, Berlin, New York pp 454–455
Wasserman RH, Taylor AN (1973) Intestinal absorption of phosphate in the chick: effect of vitamin D3 and other parameters. J Nutr 103:586–599
Paul J (1975) Cell and tissue culture. Churchill Livingstone, Great Britain, p 90
Lowry OH, Rosebrought NJ, Farr AL, Randal PJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Tovey KC, Oldham KG, Whelan JAM (1974) A simple direct assay for cyclic AMP in plasma and other biological samples using an improved competitive protein binding technique. Clin Chim Acta 56:221–234
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 277:680–685
Salomon Y, Londos C, Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58:541–548
Wallace RW, Tallant EA, Cheung WY (1983) Assay of calmodulin by Ca2+-dependent phosphodiesterase. Methods Enzymol 102:39–47
Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400
Snedecor GW, Cochran WG (1967) Statistical methods. The Iowa State University Press, Ames, Iowa
Cloix JF, d'Herbigny E, Ulmann A (1980) Renal parathyroid hormone-dependent adenylate cyclase in vitamin D-deficient rats. J Biol Chem 255:11280–11283
Barsony J, Marx SJ (1988) Receptor-mediated rapid action of 1α,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts. Proc Natl Acad Sci USA 85:1223–1226
Luchowski EM, Jousif F, Triggle DJ, Maurer SC, Sarmiento JG, Janis RA (1984) Effects of metal cations and calmodulin antagonists on [3H]-nitrendipine binding in smooth and cardiac muscle. J Pharmacol Exp Ther 230:607–613
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fernandez, L.M., Massheimer, V. & de Boland, A.R. Cyclic AMP-dependent membrane protein phosphorylation and calmodulin binding are involved in the rapid stimulation of muscle calcium uptake by 1,25-dihydroxyvitamin D3 . Calcif Tissue Int 47, 314–319 (1990). https://doi.org/10.1007/BF02555915
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02555915