Inositol Lipids and Intracellular Communication

  • Michael John Berridge
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Cells communicate with each other by means of chemical signals such as hormones and neurotransmitters. There has been a major interest in trying to unravel how cells detect these incoming signals and translate the information into the second messengers responsible for regulating many diverse physiological processes. An intracellular communication system based on the products of inositol lipid hydrolysis is central to many cellular control mech anisms. This signaling pathway is particularly responsible for altering the intracellular level of calcium, which is the major theme of this article. Initially, I shall examine how cells synthesize and hydrolyze the inositol lipid responsible for generating the second messengers inositol-1,4,5-trisphosphate (Insl,4,5P3) and diacylglycerol (DG). The way in which these two messengers function to modulate calcium homeostasis will be considered with particular emphasis on how they might interact with each other to produce a highly integrated signaling network. One consequence of such interactions is that the second messengers may oscillate at variable frequencies, which may be an important element in how they mediate their effects. Before considering these more dynamic aspects, it is necessary first to describe some basic biochemical features of this inositol lipid-signaling pathway.


Endoplasmic Reticulum Phosphatidic Acid Calcium Entry Inositol Trisphosphate External Calcium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Authi, K. S., Evenden, B. J., and Crawford, N., 1986, Metabolic and functional consequences of introducing inositol 1,4,5-trisphosphate into saponin-permeabilized human platelets, Biochem. J. 233:707–718.PubMedGoogle Scholar
  2. Batty, I. R., Nahorski, S. R., and Irvine, R. F., 1985, Rapid formation of inositol (1,3,4,5) tetrakis-phosphate following muscarinic stimulation of rat cerebral cortical slices, Biochem. J. 232:211–215.PubMedGoogle Scholar
  3. Berridge, M. J., 1987, Inositol trisphosphate and diacylglycerol: Two interacting second messengers, Ann. Rev. Biochem. 56:159–193.PubMedCrossRefGoogle Scholar
  4. Berridge, M. J., and Irvine, R. F., 1984, Inositol trisphosphate, a novel second messenger in cellular signal transduction, Nature 312:315–321.PubMedCrossRefGoogle Scholar
  5. Bitar, K. N., Bradford, P. G., Putney, J. W., and Makhlouf, G. M., 1986, Stoichiometry of contraction and Ca2+ mobilization by inositol 1,4,5-trisphosphate in isolated gastric smooth muscle cells, J. Biol. Chem. 216:16591–16596.Google Scholar
  6. Clapper, D. L., and Lee, H. C., 1985, Inositol, trisphosphate induces calcium release from nonmito-chondrial stores in sea urchin egg homogenates. J. Biol. Chem. 260:13947–13954.PubMedGoogle Scholar
  7. Cuthbertson, K. S. R., and Cobbold, P. H., 1985, Phorbol ester and sperm activate mouse oocytes by inducing sustained oscillations in cell Ca2+, Nature 316:541–542.PubMedCrossRefGoogle Scholar
  8. Downes, C. P., and Michell, R. H., 1985, Inositol phospholipid breakdown as a receptor-controlled generator of second messengers, in: Molecular Mechanisms of Transmembrane Signaling (P. Cohen and M. D. Houslay, eds.), Elsevier, New York, pp. 3–56.Google Scholar
  9. Europe-Finner, G. N., and Newell, P. C., 1985, Inositol 1,4,5-trisphosphate induces cyclic GMP formation in Dictyostelium discoideum, Biochem. Biophys. Res. Commun. 130:1115–1122.PubMedCrossRefGoogle Scholar
  10. Europe-Finner, G. N., and Newell, P. C., 1986, Inositol 1,4,5-trisphosphate and calcium stimulate actin polymerization in Dictyostelium discoideum, J. Cell. Sci. 82:41–51.PubMedGoogle Scholar
  11. Gallacher, D. V., and Morris, A. P., 1987, The receptor-regulated calcium influx in mouse subman-dibular acinar cells is sodium dependent: A patch-clamp study, J. Physiol. 384:119–130.PubMedGoogle Scholar
  12. Guillemette, G., Balla, T., Baukal, A. J., Spat, A., and Catt, K. J., 1987, Intracellular receptors for inositol 1,4,5-trisphosphate in angiotensin II target tissues, J. Biol. Chem. 262:1010–1015.PubMedGoogle Scholar
  13. Imai, A., and Gershengorn, M. C., 1987, Independent phosphatidylinositol synthesis in pituitary plasma membrane and endoplasmic reticulum, Nature 325:726–728.PubMedCrossRefGoogle Scholar
  14. Irvine, R. F., Letcher, A. J., Heslop, J. P., and Berridge, M. J., 1986, The inositol tris/tetrakisphosphate pathway: Demonstration of Ins(l,4,5)P3-3-kinase activity in animal tissues, Nature 320:631–634.PubMedCrossRefGoogle Scholar
  15. Irvine, R. F., Letcher, A. J., Lander, D. J., Heslop, J. P., and Berridge, M. J., 1987, Inositol (3,4) bisphosphate and inositol (1,3) bisphosphate in GH4 cells: Evidence for complex breakdown of inositol (1,3,4) trisphosphate, Biochem. Biophys. Res. Commun. 143:353–359.PubMedCrossRefGoogle Scholar
  16. Irvine, R. F., and Moor, R. M., 1986, Micro-injection of inositol (1,3,4,5) tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+, Biochem. J. 240:917–920.PubMedGoogle Scholar
  17. Kikkawa, U., and Nishizuka, Y., 1986, The role of protein kinase C in transmembrane signalling, Ann. Rev. Cell. Biol. 2:149–178.PubMedCrossRefGoogle Scholar
  18. Kuno, M., and Gardner, P., 1987, Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes, Nature 326:301–304.PubMedCrossRefGoogle Scholar
  19. Miyazaki, S-I., Hashimoto, N., Yoshimoto, Y., Kishimoto, T., Igusa, Y., and Hiramoto, Y., 1986, Temporal and spatial dynamics of the periodic increase in intracellular free calcium at fertilization of golden hamster eggs, Dev. Biol. 118:259–267.PubMedCrossRefGoogle Scholar
  20. Morita, K., and Kojetsu, K., 1980, Oscillation of [Ca2+ ]i-linked K+ conductance in bullfrog sympathetic ganglion cell is sensitive to intracellular anions, Nature 283:204–205.PubMedCrossRefGoogle Scholar
  21. Mustelin, T., Poso, H., and Andersson, L. C., 1986, Role of G-proteins in T cell activation: Non-hydrolyzable GTP analogues induce early ornithine decarboxylase activity in human T lymphocytes, EMBO J. 5:3287–3290.PubMedGoogle Scholar
  22. Nishizuka, Y., 1984, The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature 308:693–697.PubMedCrossRefGoogle Scholar
  23. Okada, Y., Doida, Y., Roy, G., Tsuchiya, W., Inouye, K., and Inouye, A., 1977, Oscillations of membrane potential in L cells, I. Basic characteristics. J. Membrane Biol. 35:319–335.CrossRefGoogle Scholar
  24. Poulsen, J. H., and Williams, J. A., 1976, Spontaneous repetitive hyperpolarizations from cells in the rat adenohypophysis, Nature 263:156–158.PubMedCrossRefGoogle Scholar
  25. Putney, J. W., 1986, A model for receptor-regulated calcium entry, Cell 7:1–12.Google Scholar
  26. Putney, J. W., 1987, Formation and actions of calcium-mobilizing messenger, inositol 1,4,5-trisphos-phate, Am. J. Physiol. 252:G149–G157.PubMedGoogle Scholar
  27. Rapp, P. E., and Berridge, M. J., 1981, The control of transepithelial potential oscillations in the salivary gland of Calliphora erythrocephala, J. Exp. Biol. 93:119–132.Google Scholar
  28. Storey, D. J., Shears, S. B., Kirk, C. J., and Michell, R. H., 1984, Stepwise enzymatic dephosphor-ylation of inositol 1,4,5-trisphosphate to inositol in liver, Nature 312:374–376.PubMedCrossRefGoogle Scholar
  29. Tennes, K. A., McKinney, J. S., and Putney, J. W. Jr., 1987, Metabolism of inositol 1,4,5-trisphosphate in guinea-pig hepatocytes, Biochem. J. 242:797–802.PubMedGoogle Scholar
  30. von Tscharner, W., Prod’hom, B., Baggiolini, M., and Reuter, H., 1986, Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration, Nature 324:369–372.CrossRefGoogle Scholar
  31. Vergara, J., Tsien, R. Y., and Delay, M., 1985, Inositol 1,4,5-trisphosphate: A possible chemical link in excitation-contraction coupling in muscle, Proc. Natl. Sci. U.S.A. 82:6352–6356.CrossRefGoogle Scholar
  32. Volpe, P., Salviati, G., Di Virgilio, F., and Pozzan, T., 1985, Inositol 1,4,5-trisphosphate induces calcium release from sarcoplasmic reticulum of skeletal muscle, Nature 316:347–349.PubMedCrossRefGoogle Scholar
  33. Woods, N. M., Cuthbertson, K. S. R., and Cobbold, P. H., 1986, Repetitive transient rises in cyto-plasmic free calcium in hormone-stimulated hepatocytes, Nature 319:600–602.PubMedCrossRefGoogle Scholar
  34. Yada, T., Oiki, S., Veda, S., and Okada, Y., 1986, Synchronous oscillations of the cytoplasmic Ca2+ concentration and membrane potential in cultured epithelial cells (intestine 407), Biochim. Biophys. Acta 887:105–112.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Michael John Berridge
    • 1
  1. 1.Unit of Insect Neurophysiology and Pharmacology, Department of ZoologyUniversity of CambridgeCambridgeUK

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