Skip to main content
SpringerLink
Log in

Cyclic ADP-ribose and the regulation of calcium-induced calcium release in eggs and cardiac myocytes

  • Review
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Cyclic ADP-ribose (cADPR) is a cyclic metabolite of NAD+ synthesised in cells and tissues expressing ADP-ribosyl cyclases. Although it was first discovered in sea-urchin egg extracts as a potent calcium mobilizing agent, subsequent studies have indicated that it may have a widespread action in the activation of calcium-release channels in such diverse systems as mammalian neurones, myocytes, blood cells, eggs, and plant microsomes. In this review we focus on recent work suggesting that cADPR enhances the sensitivity of ryanodine-sensitive calcium-release channels (RyRs) to activation by calcium, a phenomenon termed calcium-induced calcium release (CICR). Two roles for cADPR in calcium signaling are discussed. The first is as a classical second messenger where its levels are controlled by extracellular stimuli, and the second mode of cellular regulation is that the levels of intracellular cADPR may set the sensitivity of RyRs to activation by an influx of calcium in excitable cells. These two possible actions of cADPR are illustrated by considering the signal transduction events during the fertilization of the sea-urchin egg and the modulation of CICR during excitation-coupling in isolated guinea-pig ventricular myocytes, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lee, H. C., Walseth, T. F., Bratt, G. T., Hayes, R. N., and Clapper, D. L. (1989) Structural determination of a cyclic metabolite of NAD with intracellular calcium-mobilizing activity.J. Biol. Chem. 264, 1608–1615.

    PubMed  CAS  Google Scholar 

  2. Dargie, P. J., Agre, M. C., and Lee, H. C. (1990) Comparison of Ca2+ mobilizing activities of cyclic ADP-ribose and inositol trisphosphate.Cell Regul. 1, 279–290.

    PubMed  CAS  Google Scholar 

  3. Rusinko, N. and Lee, H. C. (1989) Widespread occurrence in animal tissues of an enzyme catalyzing the conversion of NAD+ into a cyclic metabolite with intracellular Ca2+-mobilizing activity.J. Biol. Chem. 264, 11,725–11,731.

    CAS  Google Scholar 

  4. Lee, H. C. and Aarhus, R. (1991) ADP-ribosyl cyclase: an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite.Cell Reg. 2, 203–209.

    CAS  Google Scholar 

  5. Lee, H. C. and Aarhus, R. (1993) Wide distribution of an enzyme that catalyzes the hydrolysis of cyclic ADP-ribose.Biochim. Biophys. Acta 1164, 68–74.

    PubMed  CAS  Google Scholar 

  6. Clapper, D., Walseth, T., Dargie, P., and Lee, H. C. (1987) Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate.J. Biol. Chem. 262, 9561–9568.

    PubMed  CAS  Google Scholar 

  7. Galione, A., Lee, H. C., and Busa, W. B. (1991) Ca2+-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose.Science 253, 1143–1146.

    Article  PubMed  CAS  Google Scholar 

  8. Galione, A. and Summerhill, R. S. (1996) cADP ribose as an endogenous regulator of ryanodine receptors, inRyanodine Receptors (Sorrentino, V., ed.), CRC, Boca Raton, FL, pp. 52–70.

    Google Scholar 

  9. Meszaros, L. G., Bak, J., and Chu, A. (1993) Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel.Nature 364, 76–79.

    Article  PubMed  CAS  Google Scholar 

  10. Sitsapesan, R., McGarry, S. J., and Williams, A. J. (1995) Cyclic ADP-ribose, the ryanodine receptor and Ca2+ release.Trends Pharmacol. Sci. 16, 386–391.

    Article  PubMed  CAS  Google Scholar 

  11. Walseth, T. F., Aarhus, R., Kerr, J. A., and Lee, H. C. (1993) Identification of cyclic ADP-ribose-binding proteins by photoaffinity labeling.J. Biol. Chem. 268, 26,686–26,691.

    CAS  Google Scholar 

  12. Noguchi, N., Takasawa, S., Nata, N., Tohgo, A., Kato, I., Ikehata, F., Yonekura, H., and Okamoto, H. (1997) Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes.J. Biol. Chem. 272, 3133–3136.

    Article  PubMed  CAS  Google Scholar 

  13. Lee, H. C., Aarhus, R., Graeff, R., Gurnack, M. E., and Walseth, T. F. (1994) Cyclic ADP-ribose activation of the ryanodine receptor is mediated by calmodulin.Nature 370, 307–309.

    Article  PubMed  CAS  Google Scholar 

  14. Walseth, T. F. and Lee, H. C. (1993) Synthesis and characterization of antagonists of cyclic ADP-ribose-induced Ca2+ release.Biochim. Biophys. Acta 1178, 235–242.

    Article  PubMed  CAS  Google Scholar 

  15. Ashamu, G. A., Galione, A., and Potter, B. V. L. (1995) Chemoenzymatic synthesis of analogues of the second messenger candidate cyclic adenosine 5′-diphosphate ribose.Chem. Comm. 1359–1360.

  16. Bailey, V., Summerhill, R., Galione, A., and Potter, B. V. L. (1996) Cyclic aristeromycin diphosphate ribose: a potent and poorly hydrolysable Ca2+ mobilizing mimic of cyclic adenosine diphosphate ribose.FEBS Lett. 379, 227–230.

    Article  PubMed  CAS  Google Scholar 

  17. Bailey, V., Sethi, J., Fortt, S. M., Galione, A., and Potter, B. V. L. (1997) 7-deaza-cyclic adenosine 5′-diphosphate ribose: First example of a Ca2+ mobilizing partial agonist related to cyclic adenosine 5′-diphosphate ribose.Chem. and Biol. 4, 51–61.

    Article  CAS  Google Scholar 

  18. Bailey, V. C., Sethi, J. K., Galione, A., and Potter, B. V. L. (1997) Synthesis of 7-deaza-8-bromo cyclic adenosine 5′-diphosphate ribose: first hydrolysis resistant antagonist at the cyclic adenosine 5′-diphosphate ribose receptor.Chem. Comm. 695,696.

    Google Scholar 

  19. Galione, A., McDougall, A., Busa, W., Willmott, N., Gillot, I., and Whitaker, M. (1993) Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs.Science 261, 348–352.

    Article  PubMed  CAS  Google Scholar 

  20. Whitaker, M. J. and Swann, K. (1993) Lighting the fuse at fertilization.Development 117, 1–12.

    CAS  Google Scholar 

  21. Whitaker, M. J. and Irvine, R. F. (1984) Microinjection of inositol trisphosphate activates sea urchin eggs.Nature 312, 636–638.

    Article  CAS  Google Scholar 

  22. Whitaker, M., Swann, K., and Crossley, I. (1993) What happens during the latent period at fertilization, inMechanisms of Egg Activation (Nuccitelli, R., Cherr, G.N., and Clark, W. H., Jr., ed.), Plenum, New York, pp. 157–171.

    Google Scholar 

  23. Whalley, T., McDougall, A., Crossley, I., Swann, K., and Whitaker, M. (1992) Internal calcium release and activation of sea urchin eggs by cGMP are independent of the phosphoinositide signaling pathway.Mol. Biol. Cell 3, 373–383.

    PubMed  CAS  Google Scholar 

  24. Galione, A., White, A., Willmott, N., Turner, M., Potter, B. V., and Watson, S. P. (1993) cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis.Nature 365, 456–459.

    Article  PubMed  CAS  Google Scholar 

  25. Sethi, J., Empson, R., and Galione, A. (1996) Nicotinamide inhibits cADPR-mediated calcium signalling in sea urchin eggs.Biochem. J. 319, 613–617.

    PubMed  CAS  Google Scholar 

  26. Willmott, N., Sethi, J. K., Walseth, T. F., Lee, H. C., White, A. M., and Galione, A. (1996) Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway.J. Biol. Chem. 271, 3699–3705.

    Article  PubMed  CAS  Google Scholar 

  27. Guse, A. H., Silva, C. P. D., Emmrich, F., Ashamu, G. A., Potter, B. V. L., and Mayr, G. W. (1995) Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+ release in T lymphocyte cell lines.J. Immunol. 155, 3353–3359.

    PubMed  CAS  Google Scholar 

  28. Clementi, E., Riccio, M., Sciorati, C., Nistico, G., and Meldolesi, J. (1996) The type 2 ryanodine receptor of neurosecretory PC12 cells is activated by cyclic ADP-ribose.J. Biol. Chem. 271, 17,739–17,745.

    CAS  Google Scholar 

  29. Jorgensen, T. D., Dissing, S., and Gromada, J. (1996) Cyclic GMP potentiates phenylephrine but not cyclic ADP-ribose-evoked calcium release from rat lacrimal acinar cells.FEBS Lett. 391, 117–120.

    Article  PubMed  CAS  Google Scholar 

  30. Fruen, B. R., Mickelson, J. R., Shomer, N. H., Velez, P., and Louis, C. F. (1994) Cyclic ADP-ribose does not affect cardiac or skeletal muscle ryanodine receptors.FEBS Lett. 352, 123–126.

    Article  PubMed  CAS  Google Scholar 

  31. Sitsapesan, R., McGarry, S. J., and Williams, A. J. (1994) Cyclic ADP-ribose competes with ATP for the adenine nucleotide binding site on the cardiac ryanodine receptor Ca2+-release channel.Circ. Res. 75, 596–600.

    PubMed  CAS  Google Scholar 

  32. Rakovic, S., Galione, A., Ashamu, G. A., Potter, B. V. L., and Terrar, D. A. (1996) A specific cyclic ADP-ribose antagonist inhibits cardiac excitaation-contraction coupling.Curr. Biol. 6, 989–996.

    Article  PubMed  CAS  Google Scholar 

  33. Rakovic, S. and Terrar, D. A. (1994) Possible effects of cADP-ribose on calcium transients and contractions in guinea pig isolated ventricular myocytes.J. Physiol. 475, 81P.

    Google Scholar 

  34. Iino, S., Cui, Y., Galione, A., and Terrar, D. A. (1996) Actions of cADP-ribose on contractions in guinea-pig isolated ventricular myocytes.Br. J. Pharmac. 119, 226P.

    Google Scholar 

  35. Wier, W. G. and Blatter, L. A. (1991) Ca2+-oscillations and Ca2+-waves in mammalian cardiac and vascular smooth muscle cells.Cell Calcium 12, 241–254.

    Article  PubMed  CAS  Google Scholar 

  36. Rakovic, S., Galione, A., Ashamu, G. A., Potter, B. V. L., and Terrar, D. A. (1995) Possible effects of 8-amino-cADPR on oscillating contractions and associated electrical activity in guinea-pig isolated ventricular myocytes.Japan J. Physiol. 45, S143.

    Google Scholar 

  37. Iino, S., Cui, Y., Galione A., and Terrar, D. A. (1997) Influence of temperature on the effects of cADP-ribose analogues on contraction in guinea-pig isolated ventricular myocytes.J. Physiol. 499, 32P-33P.

    Google Scholar 

  38. Guo, X., Laflamme, M. A., and Becker, P. L. (1996) Cyclic ADP-ribose does not regulate sarcoplasmic reticulum Ca2+ release in intact cardiac myocytes.Circ. Res. 79, 147–151.

    PubMed  CAS  Google Scholar 

  39. Xiao, R.-P., Valdiviaa, H., Bogdanov, K., Valdivia, C., Lakatta, E. G., and Cheng, H. (1997) The immunophilin FK506-binding protein modulates Ca2+ release channel closure in rat heart.J. Physiol. 500, 343–354.

    PubMed  CAS  Google Scholar 

  40. Timerman, A. P., Wiederrecht, G., Marcy, A., and Fleischer, S. (1995) Characterization of an exchange reaction between soluble FKBP-12 and the FKBP ryanodine receptor complex.J. Biol. Chem. 270, 2451–2459.

    Article  PubMed  CAS  Google Scholar 

  41. Meszaros, V., Socci, R., and Meszaros, L. G. (1995) The kinetics of cyclic ADP-ribose formation in heart muscle.Biochem. Biophys. Res. Commun. 210, 452–456.

    Article  PubMed  CAS  Google Scholar 

  42. Walseth, T., Aarhus, R., Zeleznikar, R., and Lee, H. C. (1991) Determination of endogenous levels of cyclic ADP-ribose in rat tissues.Biochem. Biophys. Acta 1094, 113–120.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Department of Pharmacology, Mansfield Road, OX1 3QT, Oxford, UK

    Antony Galione, Yi Cui, Ruth Empson, Shigao Iino, Heather Wilson & Derek Terrar

Authors
  1. Antony Galione
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruth Empson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shigao Iino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heather Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Derek Terrar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antony Galione.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galione, A., Cui, Y., Empson, R. et al. Cyclic ADP-ribose and the regulation of calcium-induced calcium release in eggs and cardiac myocytes. Cell Biochem Biophys 28, 19–30 (1998). https://doi.org/10.1007/BF02738307

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02738307

Index Entries

Search

Navigation