Mechanisms of Intracellular Calcium Movement Activated by Guanine Nucleotides and Inositol-1,4,5-Trisphosphate

  • Donald L. Gill
  • Julienne M. Mullaney
  • Tarun K. Ghosh
  • Sheau-Huei Chueh
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


It is now well established that the intracellular second messenger inositol-1,4,5-trisphosphate (IP3) is involved in the release of Ca2+ from a Ca2+ -sequestering organelle, widely considered to be the endoplasmic reticulum (ER) (Berridge and Irvine, 1984; Gill, 1985; Majeruset al., 1986). In a series of recent studies, we observed that a highly sensitive and specific guanine nucleotide regulatory process induces a release of Ca2+ in cells that appears very similar to that mediated by IP3(Gillet al., 1986; Uedaet al., 1986; Chueh and Gill, 1986). Our initial studies were conducted using either permeabilized cells or isolated microsomal membrane vesicles derived from the NIE-115 neuronal cell line; GTP-dependent Ca2+ release was observed to be very similar in the two preparations (Gillet al., 1986; Uedaet al., 1986). Recent studies (Henne and Söling, 1986; Jean and Klee, 1986; Chuehet al., 1987) have extended the number of diverse cell types in which the same GTP-activated Ca2+ release process is observed. In each cell type, submicromolar GTP concentrations rapidly effect a substantial release of Ca2+ sequestered via internal Ca2+ -pumping activity within a nonmitochondrial organelle, believed to be the ER. The Ca2+ -accumulating properties of this intracellular organelle have been described in detail in earlier studies with permeabilized cells (Gill and Chueh, 1985).


Guanine Nucleotide Inositol Trisphosphate Membrane Fusion Event Glioma Hybrid Cell Plasma Membrane Calcium Pump 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berridge, M. J., and Irvine, R. F., 1984, Inositol trisphosphate, a novel second messenger in cellular signal transduction, Nature 312:315–321.PubMedCrossRefGoogle Scholar
  2. Burton, P. R., and Laveri, L. A., 1985, The distribution, relationships to other organelles, and calciumsequestering ability of smooth endoplasmic reticulum in frog olfactory axons, J. Neurosci. 5: 3047–3060.PubMedGoogle Scholar
  3. Chueh, S. H., and Gill, D. L., 1986, Inositol 1,4,5-trisphosphate and guanine nucleotides activate calcium release from endoplasmic reticulum via distinct mechanisms, J. Biol. Chem. 261:13883–13886.PubMedGoogle Scholar
  4. Chueh, S. H., Mullaney, J. M., Ghosh, T. K., Zachary, A. L., and Gill, D. L., 1987, GTP and inositol 1,4,5-trisphosphate-activated intracellular calcium movements in neuronal and smooth muscle cell lines, J. Biol. Chem. 262:13857–13864.PubMedGoogle Scholar
  5. Dawson, A. P., 1985, GTP enhances inositol trisphosphate-stimulated Ca2+ release from rat liver microsomes, FEBS Lett. 184:147–150.CrossRefGoogle Scholar
  6. Dawson, A. P., Comerford, J. G., and Fulton, D. V., 1986, The effect of GTP on inositol 1,4,5-trisphosphate-stimulated Ca2+ efflux from a rat liver microsomal fraction, Biochem. J. 234:311–315.PubMedGoogle Scholar
  7. Gill, D. L., 1985, Receptors coupled to calcium mobilization, Adv. Cyclic Nucleotide Protein Phos. Res. 19:195–212.Google Scholar
  8. Gill, D. L., and Chueh, S. H., 1985, An intracellular (ATP + Mg2+ )-dependent calcium pump within the N1E-115 neuronal cell line, J. Biol. Chem. 260:9289–9297.PubMedGoogle Scholar
  9. Gill, D. L., Chueh, S. H., and Whitlow, C. L., 1984, Functional importance of the synaptic plasma membrane calcium pump and sodium-calcium exchanger, J. Biol. Chem. 259:10807–10813.PubMedGoogle Scholar
  10. Gill, D. L., Ueda, T., Chueh, S. H., and Noel, M. W., 1986, Ca2+ release from endoplasmic reticulum is mediated by a guanine nucleotide regulatory mechanism, Nature 320:461–464.PubMedCrossRefGoogle Scholar
  11. Henkart, M. P., Reese, T. S., and Brinley, F. J., 1978, Endoplasmic reticulum sequesters calcium in the squid giant axon, Science 202:1300–1303.PubMedCrossRefGoogle Scholar
  12. Henne, V., and Soling, H-D., 1986, Guanosine 5′-triphosphate releases calcium from rat liver and guinea pig parotid gland endoplasmic reticulum independently of inositol 1,4,5-trisphosphate, FEBS Lett. 202:267–273.PubMedCrossRefGoogle Scholar
  13. Hui, S. W., Isac, T., Boni, L. T., and Sen, A., 1985, Action of polyethylene glycol on the fusion of human erythrocyte membranes, J. Membrane Biol. 84:137–146.CrossRefGoogle Scholar
  14. 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
  15. Jean, B., & Klee, C. B., 1986, Calcium modulation of inositol 1,4,5-trisphosphate-induced calcium release from neuroblastoma X glioma hybrid (NG108–15) microsomes, J. Biol. Chem. 261: 16414–16420.PubMedGoogle Scholar
  16. Majerus, P. W., Connolly, T. M., Deckmyn, H., Ross, T. S., Bross, T. E., Ishii, H., Bansal, V. S., and Wilson, D. B., 1986, The metabolism of phosphoinositide-derived messenger molecules, Science 234:1519–1526.PubMedCrossRefGoogle Scholar
  17. Martonosi, A. N., 1982, Transport of calcium by sarcoplasmic reticulum, in: Calcium in Cell Function, Vol. 3 (W. Y. Cheung, ed.), Academic Press, New York, pp. 37–102.Google Scholar
  18. McGraw, C. F., Somlyo, A. V., and Blaustein, M. P., 1980, Localization of calcium in presynaptic nerve terminals. J. Cell Biol. 85:228–241.PubMedCrossRefGoogle Scholar
  19. Muallem, S., Schoeffield, M., Pandol, S., and Sachs, G., 1985, Inositol trisphosphate modification of ion transport in rough endoplasmic reticulum, Proc. Natl. Acad. Sci. USA 82:4433–4437.PubMedCrossRefGoogle Scholar
  20. Mullaney, J. M., Chueh, S. H., Ghosh, T. K., and Gill, D. L., 1987, Intracellular calcium uptake activated by GTP: Evidence for a possible guanine nucleotide-induced transmembrane conveyance of intracellular calcium, J. Biol. Chem. 262:13865–13872.PubMedGoogle Scholar
  21. Norris, J. S., Gorski, J., and Kohler, P. O., 1974, Androgen receptors in a Syrian hamster ductus deferens tumour cell line, Nature 248:422–424.PubMedCrossRefGoogle Scholar
  22. Putney, J. W., 1986, A model for receptor-regulated calcium entry, Cell Calcium 7:1–12.PubMedCrossRefGoogle Scholar
  23. Smith, J. B., Smith, L., and Higgins, B. L., 1985, Temperature and nucleotide dependence of calcium release by myo-inositol 1,4,5-trisphosphate in cultured vascular smooth muscle cells, J. Biol. Chem. 260:14413–14416.PubMedGoogle Scholar
  24. Ueda, T., Chueh, S. H., Noel, M. W., and Gill, D. L., 1986, Influence of inositol 1,4,5-trisphosphate and guanine nucleotides on intracellular calcium release within the N1E-115 neuronal cell line, J. Biol. Chem. 261:3184–3192.PubMedGoogle Scholar
  25. Wakasugi, H., Kimura, T., Haase, W., Kribben, A., Kaufmann, R., and Schulz, I., 1982, Calcium uptake into acini from rat pancreas: evidence for intracellular ATP-dependent calcium sequestration, J. Membrane Biol. 65:205–220.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Donald L. Gill
    • 1
  • Julienne M. Mullaney
    • 1
  • Tarun K. Ghosh
    • 1
  • Sheau-Huei Chueh
    • 1
  1. 1.Department of Biological ChemistryUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations