Skip to main content
SpringerLink
Log in

Guanine Nucleotides Inhibit cAMP Accumulation Induced by Metabotropic Glutamate Receptor Activation

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Metabotropic glutamate receptors (mGluRs) have been shown to modulate adenylate cyclase activity via G-proteins. In the present study we report similar results to the previously observed in the literature, showing that glutamate and the metabotropic agonists, 1S,3R-ACPD or quisqualate induced cAMP accumulation in hippocampal slices of young rats. Moreover, guanine nucleotides GTP, GDP or GMP, inhibited the glutamate-induced cAMP accumulation. By measuring LDH activity in the buffer surrounding the slices, we showed that the integrity of the slices was maintained, indicating that the effect of guanine nucleotides was extracellular. GMP, GDPβ-S or Gpp(NH)p abolished quisqualate-induced cAMP accumulation. GDPβ-S or Gpp(NH)p but not GMP inhibited 1S,3R-ACPD-induced cAMP accumulation. The response evoked by glutamate was also abolished by the mGluR antagonists: L-AP3 abolished glutamate-induced cAMP accumulation in a dose-dependent manner and MCPG was effective only at the 2 mM dose. DNQX was ineffective. We are reporting here, an inhibition induced by guanine nucleotides, via an extracellular site (s), similar to the observed with classical glutamate antagonists on a cellular response evoked by mGluR agonists.

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. Lipton, S. A., and Rosenberg, P. A. 1995. Mechanisms of Disease. Excitatory amino acids as a final common pathway for neurological disorders. The New England J. Med. 330:613-622.

    Google Scholar 

  2. Nakanishi, S., Masu, M., Bessho, Y., Nakajima, Y., Hayashi, Y., Nomura, A., and Shigemoto, R. 1994. Molecular diversity and physiological functions of glutamate receptors. Neuropsychopharmacol. 10:8S-13S.

    Google Scholar 

  3. Pin, J.-P., and Duvoisin, R. 1995. Review: Neurotransmitter receptors I. The metabotropic glutamate receptors: structure and functions. Neuropharmacol. 34:1-26.

    Google Scholar 

  4. Hepler, J. R., and Gilman, A. G., 1992. G Proteins. Trends Biochem. Sci. 17:383-387.

    PubMed  Google Scholar 

  5. Butcher, S. P., Roberts P. J., and Collins, J. F. 1986. Purine nucleotides inhibit the binding of DL-[3H]2-amino-4-phosphonobutyrate (DL-[3H]APB) to L-glutamatesensitive sites on rat brain membranes. Biochem. Pharmacol. 35:991-994.

    PubMed  Google Scholar 

  6. Monahan, J. B., Hood, W. F., Michel J., and Compton, R. P. 1988. Effects of guanine nucleotides on N-methyl-D-aspartate receptor-ligand interactions. Mol. Pharmacol. 34:111-116.

    PubMed  Google Scholar 

  7. Baron, B. M., Dudley, M. W., McCarty, D. R., Miller, F. P., Reynolds, I. J., and Schmidt, C. J. 1989. Guanine nucleotides are competitive inhibitors of N-Methyl-D-Aspartate at its receptor site both in vitro and in vivo. J. Pharmacol. Exp. Ther. 250:162-169.

    PubMed  Google Scholar 

  8. Gorodinsky, A., Paas, Y., and Teichberg, V. I. 1993. A ligand binding study of the interactions of guanine nucleotides with non-NMDA receptors. Neurochem. Int. 23:285-291.

    PubMed  Google Scholar 

  9. Paas, Y., Devillers-Thiery, A., Changeux, J.-P., Medevielle, F., and Teichberg, V.I. 1996. Identification of an extracellular motif involved in the binding of guanine nucleotides by a glutamate receptor. EMBO J. 15:1548-1556.

    PubMed  Google Scholar 

  10. Souza, D. O., and Ramirez, G. 1991. Effects of guanine nucleotides on kainic acid binding and on adenylate cyclase in chick optic tectum and cerebellum. J. Mol. Neurosci. 3:39-45.

    PubMed  Google Scholar 

  11. Barnes, J. M., Murphy, P. A., Kirkham D., and Henley, J. M. 1993. Interaction of guanine nucleotides with [3H]kainate and 6-[3H]cyano-7-nitroquinoxaline-2,3-dione binding in goldfish brain. J. Neurochem. 61:1685-1691.

    PubMed  Google Scholar 

  12. Paz, M. M., Ramos, M., Ramirez G., and Souza, D. O. 1994. Differential effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity in chick optic tectum. FEBS Letters 355:205-208.

    PubMed  Google Scholar 

  13. Budson, A. E., Jackson P. S., and Lipton, S. A. 1991. GDPβS antagonizes whole-cell current responses to excitatory amino acids. Brain Res. 548:346-348.

    PubMed  Google Scholar 

  14. Tasca, C. I., Wofchuk, S. T., Souza, D. O., Ramírez, G., and Rodnight, R. 1995. Guanine nucleotides inhibit the stimulation of GFAP phosphorylation by glutamate. NeuroReport 6:249-252.

    PubMed  Google Scholar 

  15. Schoepp, D. D., and Johnson, B. G. 1993. Metabotropic glutamate receptor modulation of cAMP accumulation in the neonatal rat hippocampus. Neuropharmacol. 32:1359-1365.

    Google Scholar 

  16. Winder, D. G., and Conn, P. J. 1995. Metabotropic glutamate receptor (mGluR)-mediated potentiation of cyclic AMP responses does not require phosphoinositide hydrolysis mediation by a group II-like mGluR. J. Nuerochem. 64:592-599.

    Google Scholar 

  17. Tasca, C. I., Vendite, D., Garcia, K. L., and Souza, D. O. 1995. Effects of adenosine on cAMP production during early development in the optic tectum of chicks. Int. J. Devl. Neurosci. 13:545-553.

    Google Scholar 

  18. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265-275.

    PubMed  Google Scholar 

  19. Tasca, C. I., Vendite, D., Martini, L. H., Cardoso L. F., and Souza, D. O. 1995. Modulation of adenosine-induced cAMP accumulation via metabotropic glutamate receptors in chick optic tectum. Neurochem. Res. 20:1033-1039.

    PubMed  Google Scholar 

  20. Romano, C., Price M. T., and Olney, J. W. 1995. Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina. J. Neurochem. 65:59-67.

    PubMed  Google Scholar 

  21. Plesner, L. 1995. Ecto-ATPases: identities and functions. Int. Rev. Citology 158:142-214.

    Google Scholar 

  22. Schoepp, D. D., Johnson, B. G., Salhoff, C. R., Wright, R. A., Goldsworthy, J. S., and Baker, S. R. 1995. Second-messenger responses in brain slices to elucidate novel glutamate receptors. J. Neurosci. Methods 59:105-110.

    PubMed  Google Scholar 

  23. O'Hara, P. J., Shepard, P. O., Thogersen, H., Venezia, D., Haldeman, B. A., McGrane, V., Houamed, K. M., Thomsen, C., Gilbert, T. L., and Mulvihill, E. R. 1993. The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron 11:41-52.

    PubMed  Google Scholar 

  24. Takahashi, K., Tsuchida, K., Tannabe, Y., Masu, M., and Nakanishi, S. 1993. Role of the large extracellular domain of metabotropic glutamate receptors in agonist selectivity determination. J. Biol. Chem. 268:19341-19345.

    PubMed  Google Scholar 

  25. Bockaert, J. 1991. G proteins and G-protein-coupled receptors: structure, function and interactions. Current Opinion in Neurobiol. 1:32-42.

    Google Scholar 

  26. Randle, J. C. R., Guet, T., Bobichon, C., Moreau, C., Curutchet, P., Lambolez, B., De Carvalho, L. P., Cordi, A., and Lepagnol, J. M. 1992. Quinoxaline derivatives: Structure-activity relationships and physiological implications of inhibition of N-Methyl-D-Aspartate and non-N-methyl-D-aspartate receptor-mediated currents and synaptic potentials. Molec. Pharmacol. 41:337-345.

    Google Scholar 

  27. Zimmermann, H. 1996. Biochemistry, localization and functional roles of ecto-nucleotidases in the nervous system. Prog. Neurobiol. 49:589-618.

    PubMed  Google Scholar 

  28. Middlemiss, P. J., Gysbers, J. W., and Rathbone, M. P. 1995. Extracellular guanosine and guanosine-5' triphosphate increase: NGF synthesis and release from cultured mouse neopallital astrocytes. Brain. Res. 677:152-156.

    PubMed  Google Scholar 

  29. Gysbers, J. W., and Rathbone, M. P. 1996. GTP and guanosine synergistically enhance NGF-induced neurite outgrowth from PC12 cells. Int. J. Devl. Neurosci. 14:19-34.

    Google Scholar 

  30. Neary, J. T., Rathbone, M. P., Cattabeni, F., Abbrachio, M. P., and Burnstock, G. 1996. Trophic actions of extracellular nucleotides and nucleosides on glial and neuronal cells. TINS. 19:13-18.

    PubMed  Google Scholar 

  31. Zetterstrom, T., Vernet, L., Ungerstedt, U., Tossman, U., Jonzon, B., and Fredholm, B. B. 1982. Purine levels in the intact rat brain. Studies with an implanted perfused hollow fibre. Neurosci. Lett. 29:111-115.

    PubMed  Google Scholar 

  32. Uemura, Y., Miller, J. M., Matson, W. R., and Beal, M. F. 1991. Neurochemical analysis of focal ischemia in rats. Stroke 22:1548-1553.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, 90035–003, Porto Alegre, RS, Brasil

    Carla I. Tasca

  2. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040–900, Florianópolis, SC, Brasil

    Carla I. Tasca & Diogo O. Souza

  3. Centro de Biologia Molecular, Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid España

    Galo Ramírez

Authors
  1. Carla I. Tasca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luciana F. Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lúcia H. Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Galo Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Diogo O. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tasca, C.I., Cardoso, L.F., Martini, L.H. et al. Guanine Nucleotides Inhibit cAMP Accumulation Induced by Metabotropic Glutamate Receptor Activation. Neurochem Res 23, 183–188 (1998). https://doi.org/10.1023/A:1022480825290

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022480825290

Search

Navigation