Glycogen Metabolism in Smooth Muscle

  • Theodore G. Sotiroudis
  • Stathis Nikolaropoulos
  • Athanasios E. Evangelopoulos
Part of the NATO ASI Series book series (NSSA, volume 133)


In the last few years there has been a surge of interest in smooth muscle biochemistry. There are two major reasons why this tissue is of particular interest. First, although the total high energy Phosphagen pool (phosphocreatine + ATP) is substantially lower than that of skeletal muscle, however energy metabolism in smooth muscle is finely tuned to meet contractile energy requirements1. Second, it has recently become evident that reversible phosphorylation of myosin, via an enzyme cascade similar to that involved in the activation of glycogen Phosphorylase, plays a major role in regulating the interaction of actin and myosin in smooth muscle2,3.


Smooth Muscle Protein Phosphatase Myosin Light Chain Glycogen Phosphorylase Glycogen Metabolism 


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  1. 1.
    R.M. Lynch and R.J. Paul, Energy metabolism and transduction in smooth muscle, Experientia 41:970 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    R.S. Adelstein, M.D. Pato and M.A. Conti, The role of phosphorylation in regulating contractile proteins, Adv.Cycl.Nucl.Res. 14:361 (1981).Google Scholar
  3. 3.
    K.E. Kamm and J.T. Stull, The function of myosin and myosin light chain kinase phosphorylation in smooth muscle, Ann.Rev.Pharmacol.Toxicol. 25:593 (1985),CrossRefGoogle Scholar
  4. 4.
    R.J. Paul, Chemical energetics of vascular smooth muscle, in:”Handbook of Physiology. The Cardiovascular System,”Am.Physiol .Soc, Bethesda, MD (1980).Google Scholar
  5. 5.
    P. Cohen, Protein phosphorylation and the control of glycogen metabolism in skeletal muscle, Phil.Trans.R.Soc.Lond.B302:13 (1983).Google Scholar
  6. 6.
    F. Huijing, Glycogen metabolism and glycogen-storage diseases, Physiol. Rev. 55:609 (1975).PubMedGoogle Scholar
  7. 7.
    R.E. Garfield and A.P. Somlyo, Structure of smooth muscle, in:”Calcium and Contractility,” A.K. Grover and E.E. Daniel, eds., The Humana Press, Inc., Clifton, New Jersey (1985).Google Scholar
  8. 8.
    S. Yonezawa and S.H. Hori, Electrophoretic studies on the Phosphorylase isozymes, J.Histochern.Cytochem. 23:745 (1975).CrossRefGoogle Scholar
  9. 9.
    E. Bueding, N. Kent and J. Fischer, Tissue specificity of glycogen Phosphorylase b of intestinal smooth muscle, J.Biol.Chem. 239:2099 (1964).PubMedGoogle Scholar
  10. 10.
    E. Mohme-Lundholm, Smooth muscle Phosphorylase and enzymes affecting its activity, Acta Physiol.Scand. 59:74 (1963).PubMedCrossRefGoogle Scholar
  11. 11.
    L.N. Viktorova and E.V. Pamensky, Glycogen Phosphorylase of smooth muscles, isolation and certain properties, Dokl.Acad.Nauk.SSSR 222: 1463 (1975).Google Scholar
  12. 12.
    L.N. Viktorova and E.V. Ramensky, Further molecular and catalytic characterization of uterine Phosphorylase b, FEBS Lett. 115:239 (1980).PubMedCrossRefGoogle Scholar
  13. 13.
    M.M. Appleman, E.G. Krebs and E.H. Fischer, Purification and properties of inactive liver Phosphorylase, Biochemistry 5:2101 (1966).PubMedCrossRefGoogle Scholar
  14. 14.
    H.D. Engers and N.B. Madsen, The effect of anions on the activity of Phosphorylase b, Biochem.Biophys.Res.Commun. 33:49 (1968).PubMedCrossRefGoogle Scholar
  15. 15.
    T.G. Sotiroudis, C.T. Cazianis, N.G. Oikonomakos and A.E. Evangelopoulos, Effect of sodium cholate on the catalytic and structural properties of Phosphorylase b, Eur.J.Biochem.131:625 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    W. Stalmans and G. Gevers, The catalytic activity of Phosphorylase b in the liver, Biochem.J. 200:327 (1981).PubMedGoogle Scholar
  17. 17.
    A.E. Melpidou and N.G. Oikonomakos, Effect of glucose-6-P on the catalytic and structural properties of glycogen Phosphorylase a FEBS Lett.154:105 (1983).CrossRefGoogle Scholar
  18. 18.
    B. Lederer and W. Stalmans, Human liver glycogen Phosphorylase.Kinetic properties and assay in biopsy specimens, Biochem.J. 159:689 (1976).PubMedGoogle Scholar
  19. 19.
    G.M. Carlson, P.J. Bechtel and D.J. Graves, Chemical and regulatory properties of Phosphorylase kinase and cyclic AMP-dependent protein kinase, Adv.Enzymol. 50:41 (1979).PubMedGoogle Scholar
  20. 20.
    P. Cohen, Phosphorylase kinase from rabbit skeletal muscle, Meth. Enzymol. 99:243 (1983).PubMedCrossRefGoogle Scholar
  21. 21.
    S. Pocinwong, H. Blum, D. Malencik and E.H. Fischer, Phosphorylase kinase from dogfish skeletal muscle. Purification and properties, Biochemistry 20:7219 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    I.E. Adreeva, G.V. Silonova, N.B. Livanova, T.B. Eronina, V.E. Morozov and B.F. Poglazov, Purification, quaternary structure and certain immunological properties of Phosphorylase kinase from chicken skeletal muscles, Biokhimiya 50:1504 (1985).Google Scholar
  23. 23.
    I.E. Andreeva, N.B. Livanova, T.B. Eronina and B.F. Poglazov, Regulatory properties of Phosphorylase kinase from chicken skeletal muscles, Biokhimiya 50:1646 (1985).Google Scholar
  24. 24.
    R.H. Cooper, H.S. Sul, E. McCullough and D.A. Walsh, Purification and properties of the cardiac isoenzyme of Phosphorylase kinase, J.Biol. Chem. 255:11794 (1980).PubMedGoogle Scholar
  25. 25.
    T.D. Chrisman, J.E. Jordan and J.H. Exton, Purification of rat liver Phosphorylase kinase, J.Biol.Chem. 257:10798 (1982).PubMedGoogle Scholar
  26. 26.
    S. Nikolaropoulos and T.G. Sotiroudis, Phosphorylase kinase from chicken gizzard. Partial purification and characterization, Eur.J.Biochem. 151:467 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    A. Tsutou, S. Nakamura, A. Negami, K. Mizuta, E. Hashimoto and H. Yamamura, Calcium- and calmodulin-dependent Phosphorylase kinase activity in porcine uterine smooth muscle, Biochem.Biophys.Res. Commun. 126:544 (1985).PubMedCrossRefGoogle Scholar
  28. 28.
    E. Ozawa, Energetics of smooth muscle, J.Jap.Med.Ass. 72:1322 (1974).Google Scholar
  29. 29.
    S. Ebashi, Ca2+ in biological systems, Experientia 41:978 (1985).PubMedCrossRefGoogle Scholar
  30. 30.
    T.J. Singh and J.H. Wang,Stimulation of glycogen Phosphorylase kinase from rabbit skeletal muscle by organic solvents, J.Biol.Chem. 254: 8466 (1979).PubMedGoogle Scholar
  31. 31.
    Z. Hessová, M. Varsanyi and L.M.G. Heilmeyer, Jr, Dual function of calmodulin (5) in Phosphorylase kinase, Eur.J.Biochem. 146:107(1985).Google Scholar
  32. 32.
    D.A. Malencik and E.H. Fischer, Structure, function and regulation of Phosphorylase kinase, in: “Calcium and Cell Function”,W.Y. Cheung, ed., Academic Press, New York (1982).Google Scholar
  33. 33.
    J.R. Vandenheede, H. DeWulf and W. Merlevede, Liver Phosphorylase b kinase. Cyclic AMP-mediated activation and properties of the partially purified rat liver enzyme, Eur.J.Biochem. 101:51 (1979).PubMedCrossRefGoogle Scholar
  34. 34.
    S. Nakamura, A. Tsutou, K. Mizuta, A. Negami, T. Nakaza, E. Hashimoto and H. Yamamura, Calcium-calmodulin-dependent activation of porcine liver Phosphorylase kinase, FEBS Lett. 159:47 (1983).PubMedCrossRefGoogle Scholar
  35. 35.
    S.D. Kill ilea and N.M. Ky, Purification and partial characterization of bovine heart Phosphorylase kinase, Arch.Biochem.Biophys. 221: 333 (1983).CrossRefGoogle Scholar
  36. 36.
    P.J. Roach, Glycogen synthase and glycogen synthase kinases, Curr.Top. Cell.Regul. 20:45 (1982).Google Scholar
  37. 37.
    H.R. Kaslow, D.D. Lesikar, D. Antwi and A.W.H. Tan, L-type glycogen synthase. Tissue distribution and electorphoretic mobility, J.Biol. Chem. 260:9953 (1985).PubMedGoogle Scholar
  38. 38.
    P. Cohen, The role of protein phosphorylation in neural and hormonal control of cellular activity, Nature 296:613 (1982).PubMedCrossRefGoogle Scholar
  39. 39.
    A. Rubulis, R.D. Jacobs and E.C. Hughes, Glycogen synthesis in mammalian uterus, Biochim.Biophys.Acta 99:584 (1965).PubMedGoogle Scholar
  40. 40.
    A. Milwidsky and A. Gutman, Glycogen metabolism of normal human myometrium and leiomyoma. Possible hormone control, Gynecol.Obstet. Invest. 15:147 (1983).PubMedCrossRefGoogle Scholar
  41. 41.
    K.-P. Huang and J.C. Robinson, Purification and properties of the glucose-6-phosphate-dependent form of human placental glycogen synthase, Arch.Biochem.Biophys. 175:583 (1976).PubMedCrossRefGoogle Scholar
  42. 42.
    R.J. Babcoc, Smooth muscle in the human placenta, Am.J.Obst.Gynec. 105:612 (1969).Google Scholar
  43. 43.
    K.K. Schlender and E.M. Reimann, Glycogen synthase kinases distribution in mammalian tissues of forms that are independent of cyclic AMP, J.Biol.Chem. 252:2384 (1977).PubMedGoogle Scholar
  44. 44.
    P.J. Silver, C. Schmidt-Silver and J. DiSalvo, β-adrenergic regulation and cAMP kinase activation in coronary arterial smooth muscle, Am.J.Physiol. 242:H177 (1982).PubMedGoogle Scholar
  45. 45.
    C.W. Scott and M.C. Mumby, Phosphorylation of typell regulatory subunit of cAMP-dependent protein kinase in intact smooth muscle, J.Biol. Chem. 260:2274 (1985).PubMedGoogle Scholar
  46. 46.
    J. DiSalvo, D. Gifford and A. Kokkinakis, A multisubstrate Ca and cyclic nucleotide independent kinase from vascular smooth muscle. Modulation of activity by polycations, Biochem.Biophys.Res.Commun. 136:789 (1986).CrossRefGoogle Scholar
  47. 47.
    J. DiSalvo, J.M. Jiang, J.R. Vandenheede and W. Merlevede, The ATPMg-dependent phosphatase is present in mammalian vascular smooth muscle, Biochem.Biophys.Res.Commun. 108:534 (1982).PubMedCrossRefGoogle Scholar
  48. 48.
    J.F. Kuo, R.G.G. Andersson, B.C. Wise, L. Mackerlova, I. Salomonsson, N.L. Brackett, N. Katoh, M. Shoji and R.W. Wrenn, Calcium-dependent protein kinase:Widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effect of phospholipid, calmodulin and trifluoperazine, Proc.Natl.Acad.Sci. USA 77:7039 (1980).PubMedCrossRefGoogle Scholar
  49. 49.
    T.S. Ingebritsen and P. Cohen, Protein phosphatases:Properties and role in cellular regulation, Science 221:331 (1983).PubMedCrossRefGoogle Scholar
  50. 50.
    M.D. Pato and E. Kerc, Purification and characterization of a smooth muscle myosin phosphatase from turkey gizzards, J.Biol.Chem. 260: 12359 (1985).PubMedGoogle Scholar
  51. 51.
    M.D. Pato, R.S. Adelstein, D. Crouch, B. Safer, T.S. Ingebritsen and P. Cohen, The protein phosphatases involved in cellular regulation. 4. Classification of two homogeneous myosin light chain phosphatases from smooth muscle as protein phosphatase-2A1 and 2C and a homogeneous protein phosphatase from reticulocytes active on protein synthesis initiation factor eIF-2 as protein phosphatase-2A2, Eur.J.Biochem. 132:283 (1983).PubMedCrossRefGoogle Scholar
  52. 52.
    D.K. Werth, J.R. Haeberle and D.R. Hathaway, Purification of a myosin phosphatase from bovine aortic smooth muscle, J.Biol.Chem. 257: 7306 (1982).PubMedGoogle Scholar
  53. 53.
    J. DiSalvo, D. Gifford and A. Kokkinakis, Modulation of aortic protein phosphatase activity by polylysin, Proc.Soc.Exp.Biol.Med. 177:24 (1984).Google Scholar
  54. 54.
    W. Merlevede, J.R. Vandenheede, J. Goris and S.-D. Yang, Regulation of ATPMg-dependent protein phosphatase, Curr.Top.Cell.Regul. 23:177 (1984).PubMedGoogle Scholar
  55. 55.
    J. DiSalvo, D. Gifford, J.R. Vandenheede and W. Merlevede, Spontaneously active and ATPMg-dependent protein phosphatase activity in vascular smooth muscle, Biochem.Biophys.Res.Commun. 111:912 (1983).CrossRefGoogle Scholar
  56. 56.
    E. Waelkens, J. Goris, J. DiSalvo and W. Merlevede, Inhibitor-1 phosphatase activity in vascular smooth muscle, Biochem.Biophys.Res. Commun. 120:397 (1984).PubMedCrossRefGoogle Scholar
  57. 57.
    J. DiSalvo, D. Gifford and A. Kokkinakis, Properties and function of a bovine aortic polycation modulated protein phosphatase, in:”Advances in Protein Phosphatases, “W. Merlevede and J. DiSalvo, eds., Leuven University Press, Leuven (1985).Google Scholar
  58. 58.
    J. DiSalvo, G. Gifford and M.J. Jiang, Properties and function of phosphatases from vascular smooth muscle, Fed.Proc. 42:67 (1983).PubMedGoogle Scholar
  59. 59.
    M.D. Pato and R.S. Adelstein, Purification and characterization of a multisubunif phosphatase from turkey gizzard smooth muscle. The effect of calmodulin binding to myosin light chain kinase on dephosphorylation. J.Biol.Chem. 258:7047 (1983).PubMedGoogle Scholar
  60. 60.
    M.D. Pato and R.S. Adelstein, Characterization of a Mg2+ -dependent phosphatase from turkey gizzard smooth muscle, J.Biol.Chem. 258: 7055 (1983).PubMedGoogle Scholar
  61. 61.
    H. Onishi, J. Umeda, H. Uchiva and S. Watanabe, Purification of gizzard myosin light chain phosphatase, and reversible changes in the ATPase and superprecipitation activities of actomyosin in the presence of purified preparations of myosin light chain phosphatase and kinase, J.Biochem. 91:265 (1982).PubMedGoogle Scholar
  62. 62.
    J. DiSalvo, E. Waelkens, D. Gifford, J. Goris and W. Merlevede, Modulation of latent protein phosphatase activity from vascular smooth muscle by Histone-Hi and polylysine, Biochem.Biophsy.Res. Commun. 117:493 (1983).CrossRefGoogle Scholar
  63. 63.
    D.H. Namm, The activation of glycogen Phosphorylase in arterial smooth muscle, J. Pharmacol.Exper.Ther. 178:299 (1971).Google Scholar
  64. 64.
    R.J. Paul and P. Hellstrand, Dissociation of Phosphorylase a activation and contractile activity in rat portal vein, Acta Physiol.Scand. 121:23 (1984).PubMedCrossRefGoogle Scholar
  65. 65.
    J. Debowy, Adrenergic regulation of phosphorolysis and hydrolysis of glycogen in smooth muscle of rabbit stomach in situ, Arch.Immunol. Ther.Exper. 25:863 (1977).Google Scholar
  66. 66.
    P.J. Silver and J.T. Stull, Regulation of myosin light chain and Phosphorylase phosphorylation in tracheal smooth muscle, J.Biol.Chem. 257:6145 (1982).PubMedGoogle Scholar
  67. 67.
    T.B. Bolton, Calcium exchange in smooth muscle, in:”Control and manipulation of calcium movement,” J.R. Parratt, ed., Raven Press, New York (1985).Google Scholar
  68. 68.
    P.E. Galvas, C. Kuettner, R.J. Paul and J. DiSalvo, Temporal relationships between isometric force, Phosphorylase and protein kinase activities in vascular smooth muscle, Proc.Soc.Exp.Biol.Med. 178:254 (1985).PubMedGoogle Scholar
  69. 69.
    P.J. Silver and J.T. Stull, Phosphorylation of myosin light chain and Phosphorylase in tracheal smooth muscle in response to KCl and carbachol, Mol.Pharmacol. 25:267 (1984).PubMedGoogle Scholar
  70. 70.
    J. Diamond, Phosphorylase, calcium and cyclic AMP in smooth muscle contraction, Am.J.Physiol. 225:930 (1973).PubMedGoogle Scholar
  71. 71.
    G. Pettersson, Effects of dinitrophenol on Phosphorylase a activity, adenine nucleotide levels and tension in rabbit colon smooth muscle, Acta Pharmacol. Toxicol. 56:302 (1985).CrossRefGoogle Scholar
  72. 72.
    T.M. Lincoln and R.M. Johnson, Possible role of cyclic GMP- dependent protein kinase in vascular smooth muscle function, Adv.Cyclic Nucleotide Res. 17:285 (1984).Google Scholar
  73. 73.
    P.J. Silver and J.T. Stull, Effect of the calmodulin antagonist, fluphenàzine, on phosphorylation of myosin and Phosphorylase in intact smooth muscle, Mol.Pharmacol. 23:655 (1983).Google Scholar
  74. 74.
    B.I. Kurganov, N.P. Sugrobova and L.S. Mil’man, Supramolecular organization of glycolytic enzymes, J.Theor.Biol. 116:509 (1985).PubMedCrossRefGoogle Scholar
  75. 75.
    S.J.W. Busby and G.K. Radda, Regulation of the glycogen Phosphorylase system. From physical measurements to biological speculations, Cur.Top.Cell.Regul. 10:89 (1976).Google Scholar
  76. 76.
    R.M. Lynch and R.J. Paul, Compartmentation of glycolytic and glycogenolytic metabolism in vascular smooth muscle, Science 222:1344 (1983).PubMedCrossRefGoogle Scholar
  77. 77.
    R.J. Paul and R.M. Lynch, Integration of metabolism and contractility in vascular smooth muscle:Role of phosphorylation-dephosphorylation mechanisms in a functionally compartmented system, in:”Advances in Protein Phosphatases,” W. Merlevede and J. DiSalvo, eds., Leuven University Press, Leuven (1985).Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Theodore G. Sotiroudis
    • 1
  • Stathis Nikolaropoulos
    • 1
  • Athanasios E. Evangelopoulos
    • 1
  1. 1.The National Hellenic Research FoundationInstitute of Biological ResearchAthensGreece

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