Metabolism of Inositol-Glycerophospholipids in Relation to Transmembrane Signalling and Calcium Mobilization

  • Hugues Chap
  • Philippe Dajeans
  • Josette Fauvel
  • Gérard Mauco
  • Monique Plantavid
  • Line Rossignol
  • Marie-Françoise Simon
  • Louis Douste-Blazy
Part of the NATO ASI Series book series (NSSA, volume 116)


Since the discovery by Hokin and Hokin1,2 of an increased turnover of phosphatidylinositol triggered in pigeon pancreatic slices by cholinergic agonists, inositol-phospholipids have been the matter of a large number of studies, which were extensively reviewed in 1975 by Miche113. In the last three years, this field gained a renewed interest starting from a series of fundamental and complementary findings, which allow to understand how inositol-phospholipid metabolism is directly linked to the mechanism of transmembrane signalling. These very new concepts were recently reviewed in several excellent papers4–7.


Phosphatidic Acid Human Platelet Phosphatidic Acid Inositol Trisphosphate Arachidonic Acid Liberation 
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  1. 1.
    M.R. Hokin and L.E. Hokin, Enzyme secretion and the incorporation of 32P into phospholipids of pancreas slices, J. Biol. Chem. 203: 967 (1953).PubMedGoogle Scholar
  2. 2.
    L.E. Hokin and M.R. Hokin, Effects of acetylcholine on the turnover of phosphoryl units in individual phospholipids of pancreas slices and brain cortex, Biochim. Biophys. Acta 18: 102 (1955).PubMedCrossRefGoogle Scholar
  3. 3.
    R.H. Michell, Inositol phosphatides and cell surface receptor function, Biochim. Biophys. Acta 415: 81 (1975).PubMedCrossRefGoogle Scholar
  4. 4.
    M.J. Berridge, Inositol trisphosphate and diacylglycerol as second messengers, Biochem. J. 220: 345 (1984).PubMedGoogle Scholar
  5. 5.
    Y. Nishizuka, The role of protein kinase C in cell surface signal transduction and tumour promotion, Nature 308: 693 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    P.W. Majerus, D.B. Wilson, T.M. Connolly, T.E. Bross and E.J. Neufeld, Phosphoinositide turnover provides a link in stimulus-response coupling, Trends Biochem. Sci.10: 168 (1985).CrossRefGoogle Scholar
  7. 7.
    L.E. Hokin, Receptors and phosphoinositide-generated second messengers, Ann. Rev. Biochem. 54: 205 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    B. Perret, H. Chap and L. Douste-Blazy, Asymmetric distribution of arachidonic acid in the plasma membrane of human platelets. A determination using purified phospholipases and a rapid method for membrane isolation, Biochim. Biophys. Acta 556: 434 (1979).PubMedCrossRefGoogle Scholar
  9. 9.
    B. Perret, M. Plantavid, H. Chap and L. Douste-Blazy, Are polyphosphoinositides involved in platelet activation ?, Biochem. Biophys. Res. Commun. 110: 660 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    G. Mauco, C.A. Dangelmaier and J.B. Smith, Inositol lipids, phosphatidate and diacylglycerol share a common stearoylarachidonoylglycerol as a common backbone in thrombin-stimulated human platelets, Biochem. J. 224: 933 (1984).PubMedGoogle Scholar
  11. 11.
    S. Rittenhouse-Simmons, Production of diglycerides from phosphatidylinositol in activated human platelets, J. Clin. Invest., 63: 580 (1979).PubMedCrossRefGoogle Scholar
  12. 12.
    G. Mauco, H. Chap and L. Douste-Blazy, Characterization and properties of a phosphatidylinositol phosphodiesterase (phospholipase C) from platelet cytosol, FEBS Lett. 100: 367 (1979).PubMedCrossRefGoogle Scholar
  13. 13.
    W. Siess and E.G. Lapetina, Properties and distribution of phosphatidylinositol-specific phospholipase C in human and horse platelets, Biochim. Biophys. Acta 752: 329 (1983).PubMedCrossRefGoogle Scholar
  14. 14.
    R. Lenstra, G. Mauco, H. Chap and L. Douste-Blazy, Studies on enzymes related to diacylglycerol production in activated platelets. I. Phosphatidylinositol-specific phospholipase C: further characterization using a simple method for determination of activity. Biochim. Biophys. Acta 792: 199 (1984).PubMedCrossRefGoogle Scholar
  15. 15.
    S. Rittenhouse, Human platelets contain phospholipase C that hydrolyzes polyphosphoinositides, Proc. Natl. Acad. Sci. USA 80: 5417 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    D.B. Wilson, T.E. Bross, W.E. Sherman, R.A. Berger and P.W. Majerus, Inositol cyclic phosphates are produced by cleavage of phosphatidylphosphoinositols (polyphosphoinositides) with purified sheep seminal vesicle phospholipase C enzymes. Proc. Natl. Acad. Sci. USA 82: 4013 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    R.F. Irvine, A.J. Letcher, D.J. Lander and C.P. Downes, Inositol tris-phosphates in carbachol-stimulated rat parotid glands, Biochem. J. 223: 237 (1984).PubMedGoogle Scholar
  18. 18.
    M.J. Berridge, Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol, Biochem. J. 212: 849 (1983).PubMedGoogle Scholar
  19. 19.
    B.W. Agranoff, P. Murthy and E.B. Seguin, Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets, J. Biol. Chem. 258: 2076 (1983).PubMedGoogle Scholar
  20. 20.
    S.P. Watson, R.T. Mc Connell and E.G. Lapetina, The rapid formation of inositol phosphates in human platelets by thrombin is inhibited by prostacyclin, J. Biol. Chem. 259: 13199 (1984).PubMedGoogle Scholar
  21. 21.
    J.D. Vickers, R.L. Kinlough-Rathbone and J.F. Mustard, Accumulation of the inositol phosphates in thrombin-stimulated, washed rabbit platelets in the presence of lithium, Biochem. J. 224: 399 (1984).PubMedGoogle Scholar
  22. 22.
    T.M. Connolly, T.E. Bross and P.W. Majerus, Isolation of a phosphomonoesterase from human platelets that specifically hydrolyzes the 5-phosphate of inositol-1,4,5-trisphosphate, J. Biol. Chem. 260: 7868 (1985).PubMedGoogle Scholar
  23. 23.
    F.L. Call II and M. Rubert, Diglyceride kinase in human platelets, J. Lipid Res 14: 466 (1973).PubMedGoogle Scholar
  24. 24.
    G. Mauco, H. Chap, M.F. Simon and L. Douste-Blazy, Phosphatidic and lysophosphatidic acid production in phospholipase C -and thrombin-treated platelets. Possible involvement of a platelet lipase, Biochimie 60: 653 (1978).PubMedCrossRefGoogle Scholar
  25. 25.
    R.L. Bell, D.A. Kennerly, N. Stanford and P.W. Majerus, Diglyceride lipase. Pathway for arachidonate release from human platelets. Proc. Natl. Acad. Sci. USA 76: 3238 (1979).PubMedCrossRefGoogle Scholar
  26. 26.
    G. Mauco, J. Fauvel, H. Chap and L. Douste-Blazy, Studies on enzymes related to diacylglycerol production in activated platelets. II. Subcellular distribution, enzymatic properties and positional specificity of diacylglycerol- and monoacylglycerol- lipases, Biochim. Biophys. Acta 796: 169 (1984).PubMedCrossRefGoogle Scholar
  27. 27.
    H. Streb, R.F. Irvine, M.J. Berridge and I. Schulz, Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate, Nature 306: 67 (1983).PubMedCrossRefGoogle Scholar
  28. 28.
    F.A. O’Rourke, S.P. Halenda, G.B. Zavoico and M.B. Feinstein, Inositol1,4,5-trisphosphate releases Ca2+ from a Ca2+- transporting membrane vesicle fraction derived from human platelets, J. Biol. Chem 260: 956 (1985).PubMedGoogle Scholar
  29. 29.
    Y. Kawahara, Y. Takai, R. Minakuchi, K. Sano and Y. Nishizuka, Phospholipid turnover as a possible transmembrane signal for protein phosphorylation during human platelet activation by thrombin, Biochem. Biophys. Res. Commun. 97: 309 (1980).PubMedCrossRefGoogle Scholar
  30. 30.
    K. Kaibuchi, Y. Takai, M. Sawamura, M. Hoshijima, T. Fujikura and Y. Nishizuka, Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation, J. Biol. Chem 258: 6701 (1983).PubMedGoogle Scholar
  31. 31.
    C.L. Ashendel, The phorbol ester receptor: a phospholipid-regulated protein kinase, Biochim. Biophys. Acta 822: 219 (1985).PubMedCrossRefGoogle Scholar
  32. 32.
    S.E. Rittenhouse and W.C. Horne, Ionomycin can elevate intraplatelet Ca2+ and activate phospholipase A without activating phospholipase C, Biochem. Biophys. Res. Commun 123: 393 (1984).PubMedCrossRefGoogle Scholar
  33. 33.
    H. Chap, J. Lloveras and L. Douste-Blazy, Action agrégeante de la phospholipase C de Clostridium welchii sur les plaquettes humaines, C.R. Acad. Sci. Paris, Ser. D 273: 1452 (1971).Google Scholar
  34. 34.
    P.K. Schick and B.P. Yu, The role of platelet membrane phospholipids in the platelet release reaction, J. Clin. Invest 54: 1032 (1974).PubMedCrossRefGoogle Scholar
  35. 35.
    H. Chap and L. Douste-Blazy, Réaction de libération plaquettaire induite par la phospholipase C, Eur. J. Biochem 48: 351 (1974).PubMedCrossRefGoogle Scholar
  36. 36.
    H. Chap, R.F.A. Zwaal and L.L.M. van Deenen, Action of highly purified phospholipases on blood platelets. Evidence for an asymmetric distribution of phospholipids in the surface membrane, Biochim. Biophys. Acta 467: 146 (1977).PubMedCrossRefGoogle Scholar
  37. 37.
    M. Hirata, E. Suematsu, T. Hashimoto, T. Hamachi and T. Koga, Release of Ca2+ from a non-mitochondrial store site in peritoneal macrophages treated with saponin by inositol-1,4,5-trisphosphate, Biochem. J 223: 229 (1984).PubMedGoogle Scholar
  38. 38.
    J.M. Gerrard, A.M. Butler, D.A. Peterson and J.G. White, Phosphatidic acid releases calcium from a platelet membrane fraction in vitro, Prostagl. Med 1: 387 (1978).CrossRefGoogle Scholar
  39. 39.
    A.M. Benton, J.M. Gerrard, T. Michiel and S.E. Kindom, Are lysophosphatidic acids or phosphatidic acids involved in stimulus activation coupling in platelets ?, Blood 60: 642 (1982).PubMedGoogle Scholar
  40. 40.
    M.F. Simon, H. Chap and L. Douste-Blazy, Platelet aggregating activity of lysophosphatidic acids is not related to their calcium ionophore properties, FEBS Lett. 166: 115 (1984).PubMedCrossRefGoogle Scholar
  41. 41.
    R.P. Holmes and N.L. Yoss, Failure of phosphatidic acid to translocate Ca2+ across phosphatidylcholine membranes, Nature 305: 637 (1983).PubMedCrossRefGoogle Scholar
  42. 42.
    J. Fauvel, H. Chap, V. Roques, S. Levy-Toledano and L. Douste-Blazy, Biochemical characterization of plasma membranes and intracellular membranes isolated from human platelets using Percoll gradients, Biochim. Biophys. Acta in press (1986).Google Scholar
  43. 43.
    C.M. Redman, Phospholipid metabolism in intact and modified erythrocyte membranes, J. Cell Biol 49: 35 (1971).PubMedCrossRefGoogle Scholar
  44. 44.
    F. Laffont, H. Chap, G. Soula and L. Douste-Blazy, Phospholipid exchange proteins from platelet cytosol possibly involved in phospholipid effect, Biochem. Biophys. Res. Commun. 102: 1366 (1981).PubMedCrossRefGoogle Scholar
  45. 45.
    P.Y. George and G.M. Helmkamp, J. Purification and characterization of a phosphatidylinositol transfer protein from human platelets, Biochim. Biophys. Acta 836: 176 (1985).PubMedCrossRefGoogle Scholar
  46. 46.
    S.M. Prescott and P.W. Majerus, The fatty acid composition of phosphatidylinositol from thrombin-stimulated platelets, J. Biol. Chem 256: 579 (1981).PubMedGoogle Scholar
  47. 47.
    M.M. Billah, E.G. Lapetina and P. Cuatrecasas, Phospholipase A2 activity specific for phosphatidic acid. A possible mechanism for the production of arachidonic acid in platelets, J. Biol. Chem 256: 5399 (1981).PubMedGoogle Scholar
  48. 48.
    M. Inoue and H. Okuyama, Phospholipase Al acting on phosphatidic acid in porcine platelet membranes, J. Biol. Chem 259: 5083 (1984).PubMedGoogle Scholar
  49. 49.
    F.L. Call II and W.J. Williams, Phosphatidate phosphatase in human platelets, J. Lab. Clin. Med 82: 663 (1973).PubMedGoogle Scholar
  50. 50.
    T. Takenawa and Y. Nagai, Purification of phosphatidylinositol-specific phospholipase C from rat liver, J. Biol. Chem 256: 6769 (1981).PubMedGoogle Scholar
  51. 51.
    S.L. Hofmann and P.W. Majerus, Identification and properties of two distinct phosphatidylinositol-specific phospholipase C enzymes from sheep seminal vesicular glands, J. Biol. Chem 257: 6461 (1982).PubMedGoogle Scholar
  52. 52.
    M. Plantavid, L. Rossignol, H. Chap and L. Douste-Blazy, Studies of endogenous polyphosphoinositide hydrolysis in human platelet membranes. Evidence that polyphosphoinositides remain unaccessible to phosphodiesterase in the native membrane, Biochim. Biophys. Acta in press (1986).Google Scholar
  53. 53.
    T.J. Rink, S.W. Smith and R.Y. Tsien, Cytoplasmic free Ca2+ in human platelets: Ca2+ thresholds and Ca-independent activation for shape change and secretion, FEBS Lett. 148: 21 (1982).PubMedCrossRefGoogle Scholar
  54. 54.
    P.C. Johnson, J.A. Ware, P.B. Cliveden, M. Smith, A.M. Dvorak and E.W.Salzman, Measurement of ionized calcium in blood platelets with the photoprotein aequorin. Comparison with quin 2, J. Biol. Chem. 260: 2069 (1985).PubMedGoogle Scholar
  55. 55.
    M.F. Simon, H. Chap and L. Douste-Blazy, Activation of phospholipase C in thrombin-stimulated platelets does not depend on cytoplasmic free calcium concentration, FEBS Lett. 170: 43 (1984).PubMedCrossRefGoogle Scholar
  56. 56.
    J.A. Creba, C.P. Downes, P.T. Hawkins, G. Brewster, R.H. Michell and C.J. Kirk, Rapid breakdown of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones, Biochem. J 212: 733 (1983).PubMedGoogle Scholar
  57. 57.
    R.J. Haslam and M.M.L. Davidson, Potentiation by thrombin of the secretion of serotonin from permeabilized platelets equilibrated with Ca2+ buffers. Relationship to protein phosphorylation and diacylglycerol formation, Biochem. J 222: 351 (1984).PubMedGoogle Scholar
  58. 58.
    R.J. Haslam and M.M.L. Davidson, Receptor-induced diacylglycerol formation in permeabilized platelets; possible role for a GTP-binding protein, J. Receptor Res 4: 605 (1984).Google Scholar
  59. 59.
    S. Cockroft and B. Gomperts, Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase, Nature 314: 534 (1985).CrossRefGoogle Scholar
  60. 60.
    I. Litosch, C. Wallis and J.N. Fain, 5-hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands. Evidence for a role of GTP in coupling receptor activation to phosphoinositide breakdown, J. Biol. Chem 260: 5464 (1985).PubMedGoogle Scholar
  61. 61.
    M.A. Wallace and J.N. Fain, Guanosine 5′-0-thiotriphosphate stimulates phospholipase C activity in plasma membranes of rat hepatocytes, J. Biol. Chem 260: 9527 (1985).PubMedGoogle Scholar
  62. 62.
    R.J. Uhing, H. Jiang, V. Prpic and J.H. Exton, Regulation of a liver plasma membrane phosphoinositide phosphodiesterase by guanine nucleotides and calcium, FEES Lett. 188: 317 (1985).CrossRefGoogle Scholar
  63. 63.
    J.B. Smith, C. Dangelmaier and G. Mauco, Measurement of arachidonic acid liberation in thrombin-stimulated human platelets. Use of agents that inhibit both the cyclooxygenase and lipoxygenase enzymes, Biochim. Biophys. Acta 835: 344 (1985).PubMedCrossRefGoogle Scholar
  64. 64.
    H. Chap, M.F. Simon, J. Fauvel, M. Plantavid, G. Mauco and L. Douste-Blazy, Relationship between phospholipid metabolism and intracellular calcium mobilization during platelet activation. Nouv. Rev. Fr. Hématol 27: 229 (1985).PubMedGoogle Scholar
  65. 65.
    M.F. Simon, H. Chap and L. Douste-Blazy, Selective inhibition of human platelet phospholipase A2 by buffering cytoplasmic calcium with the fluorescent indicator quin 2. Evidence for different calcium sensitivities of phospholipase A2 and C, Biochim. Biophys. Acta, in press (1986).Google Scholar
  66. 66.
    W.K. Pollock, R.A. Armstrong, L.J. Brydon, R.L. Jones and D.E. Mac Intyre, Thromboxane-induced phosphatidate formation in human platelets. Relationship to receptor occupancy and to changes in cytosolic free calcium, Biochem. J 219: 833 (1984).PubMedGoogle Scholar
  67. 67.
    W. Siess, B. Boehlig, P.C. Weber and E.G. Lapetina, Prostaglandin endoperoxide analogues stimulate phospholipase C and protein phosphorylation during platelet shape change, Blood 65: 1141 (1985).PubMedGoogle Scholar
  68. 68.
    G. Mauco, H. Chap and L. Douste-Blazy, Platelet activating factor (PAFacether) promotes an early degradation of phosphatidylinositol-4,5bisphosphate in rabbit platelets, FEBS Lett. 153: 361 (1983).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Hugues Chap
    • 1
  • Philippe Dajeans
    • 1
  • Josette Fauvel
    • 1
  • Gérard Mauco
    • 1
  • Monique Plantavid
    • 1
  • Line Rossignol
    • 1
  • Marie-Françoise Simon
    • 1
  • Louis Douste-Blazy
    • 1
  1. 1.Biochimie des Lipides, Hôpital PurpanINSERM Unité 101ToulouseFrance

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