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Induction of glycogenolysis in cultured Ewing's sarcoma cells by dopamine and β-adrenergic agonists

  • Original Papers
  • Experimental Oncology
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Summary

This study describes hormonal regulation of glycogen metabolism in Ewing's sarcoma cells. 3H-Glycogen synthesized in cultured Ewing's sarcoma WE-68 cells from 3H-glucose was hydrolyzed in a concentration-dependent manner by various catecholamines. The order of potency for the glycogenolytic effects of catecholamines was isoproterenol ≧ dopamine > norepinephrine > epinephrine. The concentrations giving half-maximal effectiveness (EC50) were about 2×10-8 M, 3×10-8 M, 8×10-8 M, and 5×10-7 M for isoproterenol, dopamine, norepinephrine, and epinephrine, respectively. Higher concentrations of each of the catecholamines were necessary to elicit EC50 stimulation of cyclic AMP production in Ewing's sarcoma cells. Glycogenolysis induced by dopamine was blocked by chlorpromazine, a dopamine D1-receptor antagonist, but not by haloperidol, a dopamine D2-receptor antagonist. The glycogenolytic action of norepinephrine was markedly reduced by propranolol, a β-adrenoreceptor antagonist, and was not affected by yohimbine, an α-adrenoreceptor antagonist. In addition, chlorpromazine also antagonized the glycogenolytic response to norepinephrine. Dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, and the diterpene forskolin were also found to induce 3H-glycogen hydrolysis. Our data indicate that cate-cholamines exert their glycogenolytic effects in Ewing's sarcoma cells by stimulation of cyclic AMP formation via β-adrenergic recepetors and dopamine D1-receptors.

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References

  • Brunton LL, Hayes JS, Mayer SE (1981) Functional compartmentation of cyclic AMP and protein kinase in heart. Adv Cyclic Nucleotide Res 14:391–397

    PubMed  Google Scholar 

  • Daly JW (1984) Forskolin, adenylate cyclase, and cell physiology: an overview. Adv Cyclic Nucleotide Res 17:81–90

    Google Scholar 

  • Dellagi K, Lipinski M, Paulin D, Portier MM, Lenoir GM, Brouet JC (1987) Characterization of intermediate filaments expressed by Ewing tumor cell lines. Cancer Res 47:1170–1173b

    PubMed  Google Scholar 

  • Dreyfuss G, Schwartz KJ, Blout ER (1978) Compartmentalization of cyclic AMP-dependent protein kinases in human erythrocytes. Proc Natl Acad Sci USA 75:5926–5930

    PubMed  Google Scholar 

  • Ewing J (1921) Diffuse endothelioma of bone. Proc NY Pathol Soc 21:17–24

    Google Scholar 

  • Friedman B, Hanaoka H (1971) Round cell sarcomas of bone. A light and electron microscopic study. J Bone Joint Surg 53A: 1118–1136

    Google Scholar 

  • Hou-Jensen K, Priori E, Dmochowski L (1972) Studies on ultrastructure of Ewing's sarcoma of bone. Cancer 29:280–286

    PubMed  Google Scholar 

  • Lipinski M, Braham K, Philip I, Wiels J, Philip T, Dellagi K, Goridis C, Lenoir GM, Tursz T (1986) Phenotypic characterization of Ewing sarcoma cell lines with monoclonal antibodies. J Cell Biochem 31:289–296

    PubMed  Google Scholar 

  • Lipinski M, Braham K, Philip I, Wiels J, Philip T, Goridis C, Lenoir GM, Tursz T (1987) Neuroectoderm-associated antigens on Ewing's sarcoma cell lines. Cancer Res 47:183–187

    PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  Google Scholar 

  • Miettinen M, Lehto VP, Virtanen I (1982) Histogenesis of Ewing's sarcoma. An evaluation of intermediate filaments and endothelial cell markers. Virchow Arch [Cell Pathol] 41:277–284

    Google Scholar 

  • Moll R, Lee I, Gould VE, Berndt R, Roessner A, Franke WW (1987) Immunocytochemical analysis of Ewing's tumors. Patterns of expression of intermediate filaments and desmosomal proteins indicate cell type heterogeneity and pluripotential differentiation. Am J Pathol 127:280–304

    Google Scholar 

  • Mrsulja BB (1972a) The influence of some biogenic amines and cyclic N-2-O-dibutyryl-adenosine-3′, 5′-monophosphate on glycogen content in rat brain slices. Experientia 28:1067

    PubMed  Google Scholar 

  • Mrsulja BB (1972b) The influence of propranolol and dibenzyline on glycogenolytic effects of some biogenic amines in rat brain slices. Experientia 28:1072–1073

    PubMed  Google Scholar 

  • Mrsulja BB (1973) The influence of antistine on glycogenolytic effects of some biogenic amines in rat brain slices. Experientia 29:76–77

    PubMed  Google Scholar 

  • Nahorski SR, Rogers KJ (1972) An enzymic fluorometric micro method for determination of glycogen. Anal Biochem 49:492–497

    PubMed  Google Scholar 

  • Navas-Palacios JJ, Aparicio-Duque R, Valdes MD (1984) On the histogenesis of Ewing's sarcoma. An ultrastructural immunohistochemical, and cytochemical study. Cancer 53:1882–1901

    PubMed  Google Scholar 

  • Okajima F, Ui M (1976) Lack of correlation between hormonal effects on cyclic AMP and glycogenolysis in rat liver. Arch Biochem Biophys 175:549–557

    PubMed  Google Scholar 

  • Opler LA, Makman MH (1972) Mediation by cyclic AMP of hormone-stimulated glycogenolysis in cultured rat astrocytoma cells. Biochem Biophys Res Commun 46:1140–1145

    PubMed  Google Scholar 

  • Passonneau JV, Crites SK (1976) Regulation of glycogen metabolism in astrocytoma and neuroblastoma cells in culture. J Biol Chem 251:2015–2022

    PubMed  Google Scholar 

  • Quach TT, Rose C, Schwartz JC (1978) 3H-Glycogen hydrolysis in brain slices: response to neurotransmitters and modulation of noradrenaline receptors. J Neurochem 30:1335–1341

    PubMed  Google Scholar 

  • Reynolds CP, Smith RG, Frenkel EP (1981) The diagnostic dilemma of the “small round cell neoplasm”: catecholamine fluoresence and tissue culture morphology as markers for neuroblastoma. Cancer 48:2088–2094

    PubMed  Google Scholar 

  • Rice RW, Cabot A, Johnston AD (1973) The application of electron microscopy to the diagnostic differentiation of Ewing's sarcoma and reticulum cell sarcoma of bone. Clin Orthop 91:174–185

    PubMed  Google Scholar 

  • Rousset M, Paris H, Chevalier G, Terrain B, Mrat JC, Zweibaum A (1984) Growth-related enzymatic control of glycogen metabolism in cultured human tumor cells. Cancer Res 44:154–160

    PubMed  Google Scholar 

  • Rozengurt E (1981) Cyclic AMP: a growth-promoting signal for mouse 3T3 cells. Adv Cyclic Nucleotide Res 14:429–442

    PubMed  Google Scholar 

  • Scarpa S, D'Orazi G, Modesti M, Modesti A (1987) Ewing's sarcoma lines synthesize laminin and fibronectin. Virchows Arch [A] 410:375–381

    Google Scholar 

  • Sceman P (1981) Brain dopamine receptors. Pharmacol Rev 32:229–313

    Google Scholar 

  • Soderling TR, Park CR (1974) Recept advances in glycogen metabolism. Adv Cyclic Nucleotide Res 4:284–333

    Google Scholar 

  • Sølling H, Esman V (1975) A sensitive method of glycogen determination in the presence of interfering substances utilizing the filter-paper technique. Anal Biochem 68:664–668

    PubMed  Google Scholar 

  • Terasaki WL, Brooker G (1977) Cardiac adenosine 3′:5′-monophosphate. Free and bound forms in the isolated rat atrium. j Biol Chem 252:1041–1050

    PubMed  Google Scholar 

  • Triche TJ, Ross WE (1978) Glycogen containing neuroblastoma with clinical and histopathologic features of Ewing's sarcoma. Cancer 41:1425–1432

    PubMed  Google Scholar 

  • Van Valen F, Keck E (1987a) Functional dopamine receptors on Ewing's sarcoma cells. 3. Tagung der Deutsche Gesellschaft für Osteologie, 7–10 October 1987, Stuttgart, Abstract

  • Van Valen F, Keck E (1987b) Gold(III) inhibits activated human osteosarcoma adenylate cyclase by an action at or near the catalytic component. Biochem Biophys Res Commun 144:1109–1115

    PubMed  Google Scholar 

  • Van Valen F, Jürgens H, Winkelmann W, Keck E (1987) β-Adrenergic agonist- and prostaglandin-mediated regulation of cAMP levels in Ewing's sarcoma cells in culture. Biochem Biophys Res Commun 146:685–691

    PubMed  Google Scholar 

  • Wilkening D, Makman MH (1976) Stimulation of glycogenolysis in rat caudate nucleus slices by l-isopropylnorepinephrine, dibutyryl cyclic AMP and 2-chloroadenosine. J Neurochem 26:923–928

    PubMed  Google Scholar 

  • yarimagan HS, Bor NM (1981) The effects of epinephrine on guinea pig placental glycogen metabolism and on cellular cyclic AMP. Biochem Med 25:125–134

    Article  PubMed  Google Scholar 

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  1. Medizinische Klinik und Poliklinik C der Universität Düsseldorf, Moorenstrasse 5, D-4000, Düsseldorf, Federal Republic of Germany

    F. van Valen & E. Keck

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  1. F. van Valen
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  2. E. Keck
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van Valen, F., Keck, E. Induction of glycogenolysis in cultured Ewing's sarcoma cells by dopamine and β-adrenergic agonists. J Cancer Res Clin Oncol 114, 266–272 (1988). https://doi.org/10.1007/BF00405832

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  • DOI: https://doi.org/10.1007/BF00405832

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