Periodicity and Chaos in cAMP, Hormonal, and Ca2+ Signalling

  • A. Goldbeter
  • Y. X. Li
  • G. Dupont
Part of the NATO ASI Series book series (NSSB, volume 270)


Rhythmic, pulsatile signals are repeatedly encountered in intercellular communication (Goldbeter, 1988, 1990). Besides neurons and muscle cells which communicate by trains of electrical impulses, examples range from the generation of cyclic AMP (cAMP) pulses in the slime mold Dictyostelium discoideum (Gerisch, 1987) to the pulsatile release of a large number of hormones (Crowley and Hofler, 1987; Wagner and Filicori, 1987). While in all these instances the oscillatory dynamics characterizes the extracellular signal, recent observations indicate that signal transduction itself may be based on oscillations of intracellular messengers. Thus, many hormones or neurotransmitters act on target cells by triggering a train of intracellular Ca2+ spikes (Berridge et al., 1988).


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  1. Bassett, N.S., and Gluckman, P.D., 1986, Pulsatile growth hormone secretion in the ovine fetus and neonatal lamb, J. Endocr., 109:307–312.CrossRefPubMedGoogle Scholar
  2. Belchetz, P.E., Plant, T.M., Nakai, Y., Keogh, E.J., and Knobil, E., 1978, Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone, Science. 202:631–633.CrossRefPubMedGoogle Scholar
  3. Berridge, M.J., and Galione, A., 1988, Cytosolic calcium oscillators, FASEB J., 2:3074–3082.CrossRefPubMedGoogle Scholar
  4. Berridge, M. J., Cobbold, P. H., and Cuthbertson, K.S.R., 1988, Spatial and temporal aspects of cell signalling Phil.Trans. R. Soc. Lond. B., 320:325–343.CrossRefGoogle Scholar
  5. Borges, J.L.C., Blizzard, R.M., Evans, W.S., Furlanetto, R., Rogol, A.D., Kaiser D. L., Rivier, I, Vale, W., and Thorner, M.O,1984, Stimulation of growth hormone (GH) and somatomedin C in idiopathic GH-deficient subjects by intermittent pulsatile administration of synthetic human pancreatic tumor GH-releasing factor, J. Clin. Endocr. Metabol., 59:1–6.CrossRefGoogle Scholar
  6. Brewitt, B., and Clark, J.I., 1988, Growth and transparency in the lens, an epithelial tissue, stimulated by pulses of PDGF, Science, 242:777–779.CrossRefPubMedGoogle Scholar
  7. Cazalis, M., Dayanithi, G., and Nordmann, J. J., 1985, The role of patterned burst and interburst interval on the excitation-coupling mechanism in the isolated rat neural lobe, J. Phvsiol. Lond., 369:45–60.CrossRefGoogle Scholar
  8. Crowley, W.F., and Hofler, J.G., eds, 1987, “The Episodic Secretion of Hormones,” Wiley, New York.Google Scholar
  9. Cuthbertson, K.S.R., 1989, Intracellular calcium oscillators, in: “Cell to Cell Signalling: From Experiments to Theoretical Models”, A. Goldbeter, ed., Academic Press, London, pp. 435–447.CrossRefGoogle Scholar
  10. Darmon, M., Brächet, P., and Pereira da Silva, L.H., 1975, Chemotactic signals induce cell differentiation in Dictyostelium discoideum, Proc. Natl. Acad. Sci. USA, 72:3163–3166.CrossRefPubMedGoogle Scholar
  11. Decroly, O., and Goldbeter, A., 1982, Birhythmicity, chaos, and other patterns of temporal self-organization in a multiply regulated biochemical system, Proc. Natl. Acad. Sci. USA. 79:6917–6921.CrossRefPubMedGoogle Scholar
  12. Dupont, G., and Goldbeter, A., 1989, Theoretical insights into the origin of signal-induced calcium oscillations, in: “Cell to Cell Signalling: From Experiments to Theoretical Models”, A. Goldbeter, ed., Academic Press, London, pp. 461–474.CrossRefGoogle Scholar
  13. Dupont, G., Berridge, M.J., and Goldbeter, A., 1990, Latency correlates with period in amodel for signal-induced Ca2+ oscillations based on Ca2+-induced Ca2+ release, Cell Regul., 1: in press.Google Scholar
  14. Durston, A.J., 1974, Pacemaker mutants of Dictyostelium discoideum, Dev. Biol., 38:308–319.CrossRefPubMedGoogle Scholar
  15. Endo, M., Tanaka, M., and Ogawa, Y., 1970, Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibers, Nature, 228:34–36.CrossRefPubMedGoogle Scholar
  16. Fabiato, A., 1983, Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum, Amer. J. Physiol., 245:C1–C14.CrossRefPubMedGoogle Scholar
  17. Gerisch, G., 1987, Cyclic AMP and other signals controlling cell development and differentiation in Dictyostelium, Annu. Rev. Biochem., 56:853–879.CrossRefPubMedGoogle Scholar
  18. Gerisch, G., and Wick, U., 1975, Intracellular oscillations and release of cyclic AMP from Dictyostelium cells, Biochem. Biophys. Res. Commun., 65:364–370.CrossRefPubMedGoogle Scholar
  19. Gerisch, G., Fromm, H., Huesgen, A., and Wick, U., 1975, Control of cell contact sites by cAMP pulses in differentiating Dictyostelium cells, Nature, 255:547–549.CrossRefPubMedGoogle Scholar
  20. Ginsburg, G., and Kimmel, A.R., 1989, Inositol trisphosphate and diacylglycerol can differentially modulate gene expressiion in Dictyostelium, Proc. Natl. Acad. Sci. USA, 86:9332–9336.CrossRefPubMedGoogle Scholar
  21. Goldbeter, A., 1990, “Rythmes et Chaos dans les Systèmes Biochimiques et Cellulaires,” Masson, Paris.Google Scholar
  22. Goldbeter, A., Decroly, O., Li, Y.X., Martiel, J.L., and Moran, F., 1988, Finding complex oscillatory phenomena in biochemical systems. An empirical approach, Biophys. Chem., 29:211–217.CrossRefPubMedGoogle Scholar
  23. Goldbeter, A., and Li, Y.X., 1989, Frequency coding in intercellular communication, in: “Cell to Cell Signalling: From Experiments to Theoretical Models”, A. Goldbeter, ed., Academic Press, London, pp.461–474.Google Scholar
  24. Goldbeter, A., Dupont, G., and Berridge, M.J., 1990, Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation, Proc. Natl. Acad. Sci. USA, 87:1461–1465.CrossRefPubMedGoogle Scholar
  25. Goldbeter, A., and Wurster, B., 1989, Regular oscillations in suspensions of a putatively chaotic mutant of Dictyostelium discoideum, Experientia, 45:363–365.CrossRefPubMedGoogle Scholar
  26. Halloy, J., Li, Y.X., Martiel, J.L., Wurster, B., and Goldbeter, A., 1990, Coupling chaotic and periodic cells results in a period-doubling route to chaos in a model for cAMP oscillations in Dictyostelium suspensions, Phys. Lett. A, in press.CrossRefGoogle Scholar
  27. Hesch, R.D., 1990, Thyroid growth — An example of modulation of cell function, Hormone and Metab. Res., Suppl. Ser. Vol. 23: 47–50.Google Scholar
  28. Knobil, E., 1980, The neuroendocrine control of the menstrual cycle, Recent Progr. Horm. Res., 36:53–88.PubMedGoogle Scholar
  29. Knobil, E., 1981, Patterns of hormone signals and hormone action, New Engl. J. Med., 305:1582–1583.CrossRefPubMedGoogle Scholar
  30. Kuba, K., and Takeshita, S., 1981, Simulation of intracellular Ca2+ oscillations in a sympathetic neurone. J. Theor. Biol., 93:1009–1031.CrossRefPubMedGoogle Scholar
  31. Lemmer, B., ed., 1989, “Chronopharmacology: Cellular and Biochemical Interactions,” M. Dekker, New York and Basel.Google Scholar
  32. Leyendecker, G. L., Wildt, L., and Hansmann, M., 1980, Pregnancies following intermittent (pulsatile) administration of GnRH by means of a portable pump (“Zyklomat”): a new approach to the treatment of infertility in hypothalamic amenorrhea, J. Clin. Endocr, Metab., 51:1214–1216.CrossRefGoogle Scholar
  33. Li, Y.X., and Goldbeter, A., 1989, Frequency specificity in intercellular communication: The influence of patterns of periodic signaling on target cell responsiveness, Biophys. J., 55:125–145.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Li, Y.X., and Goldbeter, A., 1990, Frequency encoding of pulsatile signals of cAMP based on receptor desensitization in Dictyostelium cells, J. Theor. Biol., 146:355–367.CrossRefPubMedGoogle Scholar
  35. Li, Y.X., Halloy, J., Martiel, J.L., Wurster, B., and Goldbeter, A., 1990, Suppression of chaos by a tiny proportion of periodic cells in a model for cAMP signalling in Dictyostelium, submitted for publication.Google Scholar
  36. Loomis, W.F., 1975, “Dictyostelium discoideum: A Developmental System,” Academic Press, New York.Google Scholar
  37. Martiel, J. L., and Goldbeter, A., 1985, Autonomous chaotic behaviour of the slime mould Dictyostelium discoideum predicted by a model for cyclic AMP signalling, Nature, 313:590–592.CrossRefPubMedGoogle Scholar
  38. Martiel, J. L., and Goldbeter, A., 1987, A model based on receptor desensitization for cyclic AMP signaling in Dictyostelium cells, Biophys. J., 52:807–828.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Meyer, T., and Stryer, L., 1988, Molecular model for receptor-stimulated calcium spiking, Proc. Natl. Acad. Sci. USA, 85:5051–5055.CrossRefPubMedGoogle Scholar
  40. Monk, P.B., and Othmer, H.G., 1990, Wave propagation in aggregation fields of the cellular slime mould Dictyostelium discoideum, Proc. R. Soc. Lond. B, 240:555–589.CrossRefGoogle Scholar
  41. Nanjundiah, V., 1988, Periodic stimuli are more successful than randomly spaced ones for inducing development in Dictyostelium discoideum, Biosci. Rep., 8:571–577.CrossRefPubMedGoogle Scholar
  42. Rapp, P.E., 1987, Why are so many biological systems periodic? Progr. Neurobiol., 29:261–273.CrossRefGoogle Scholar
  43. Rapp, P.E., Mees, A.I., and Sparrow, C.T., 1981, Frequency encoded biochemical regulation is more accurate than amplitude dependent control, J. Theor. Biol., 90:531–544.CrossRefPubMedGoogle Scholar
  44. Roos, W., Nanjundiah, V., Malchow, D., and Gerisch, G., 1975, Amplification of cyclic-AMP signals in aggregating cells of Dictyostelium discoideum. FEBS Lett., 53:139–142.CrossRefPubMedGoogle Scholar
  45. Segel, L.A., Goldbeter, A., Devreotes, P.N., and Knox, B.E., 1986, A mechanism for exact sensory adaptation based on receptor modification, J. Theor. Biol., 120:151–179.CrossRefPubMedGoogle Scholar
  46. Simon, M.N., Driscoll, D., Mutzel, R., Part, D., Williams, J., and Veron, M., 1989, Overproduction of the regulatory subunit of the cAMP-dependent protein kinase blocks the differentiation of Dictyostelium discoideum, EMBO J., 8:2039–2034.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Monk, P.B., and Othmer, H.G., 1990, Wave propagation in aggregation fields of the cellular slime mould Dictyostelium discoideum, Proc. R. Soc. Lond. B, 240:555–589.CrossRefGoogle Scholar
  48. Snaar-Jagalska, B.E., and Van Haastert, P.J.M., 1990, Pertussis toxin inhibits cAMP-induced desensitization of adenylate cyclase in Dictyostelium discoideum, Mol. Cell. Biochem., 92:177–189.CrossRefPubMedGoogle Scholar
  49. Stojilkovic, S.S., Rojas, E., Stutzin, A., Izumi, S.-L, and Catt, K.J., 1989, Desensitization of pituitary gonadotropin secretion by agonist-induced inactivation of voltage-sensitive calcium channels, J. Biol. Chem., 264:10939–10942.PubMedGoogle Scholar
  50. Tyson, J.J., Alexander, K.A., Manoranjan, V.S., and Murray, J.D., 1989, Cyclic-AMP waves during aggregation of Dictyostelium amoebae, Physica, 34D: 193–207.Google Scholar
  51. Vaughan, R., and Devreotes, P.N., 1988, Ligand-induced phosphorylation of the cAMP receptor from Dictyostelium discoideum, J. Biol. Chem., 263:14538–14543.PubMedGoogle Scholar
  52. Wagner, T.O.F., and Filicori, M., eds, 1987, “Episodic Hormone Secretion: From Basic Science to Clinical Application,” TM-Verlag, Hameln (FRG).Google Scholar
  53. Weigle, D.S., 1987, Pulsatile secretion of fuel-regulatory hormones, Diabetes, 36:764–775.CrossRefPubMedGoogle Scholar
  54. Whim, M.D., and Lloyd, P.E., 1989, Frequency-dependent release of peptide cotransmitters from identified cholinergic motor neurons in Aplysia, Proc. Natl. Acad. Sci. USA, 86: 9034–9038.CrossRefPubMedGoogle Scholar
  55. Woods, N.M., Cuthbertson, K.S.R., and Cobbold, P.H., 1987, Agonist-induced oscillations in cytoplasmic free calcium concentration in single rat hepatocytes, Cell Calcium, 8:79–100.CrossRefPubMedGoogle Scholar
  56. Wurster, B., 1982, On induction of cell differentiation by cyclic AMP pulses in Dictyostelium discoideum, Biophys. Struct. Media., 9:137–143.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • A. Goldbeter
    • 1
  • Y. X. Li
    • 1
  • G. Dupont
    • 1
  1. 1.Faculté des SciencesUniversité Libre de BruxellesBrusselsBelgium

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