Skip to main content
Log in

Modulation of adenosine-induced cAMP accumulation via metabotropic glutamate receptors in chick optic tectum

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Changes on cyclic adenosine monophosphate (cAMP) levels in response to adenosine and glutamate and the subtype of glutamate receptors involved in this interaction were studied in slices of optic tectum from 3-day-old chicks. cAMP accumulation mediated by adenosine (100 μM) was abolished by 8-phenyltheophylline (15 uM). Glutamate and the glutamatergic agonists kainate or trans-d,l-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) did not evoke cAMP accumulation. Glutamate blocked the adenosine response in a dose-dependent manner. At 100 μM, glutamate did not inhibit the effect of adenosine. The 1 mM and 10 mM doses of glutamate inhibited adenosine-induced cAMP accumulation by 55% and 100%, respectively. When glutamatergic antagonists were used, this inhibitory effect was not affected by 200 μM 6,7-dihydroxy-2,3,dinitroquinoxaline (DNQX), an ionotropic antagonist, and was partially antagonized by 1 mM (rs)-alpha-methyl-4-carboxyphenylglycine [(rs)M-CPG], a metabotropic, antagonist, while 1 mMl-2-amino-3-phosphonopropionate (l-AP3) alone, another metabotropic antagonist, presented the same inhibitory effect of glutamate. Kainate (10 mM) and trans-ACPD (100 μM and 1 mM) partially blocked the adenosine response. This study indicates the involvement of metabotropic glutamate receptors in adenylate cyclase inhibition induced by glutamate and its agonists trans-ACPD and kainate.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

ADO:

adenosine

DNQX:

6,7-dihydroxy-2,3-dinitro-quinoxaline

KA:

kainate

l-AP3:

l-2-amino-3-phosphonopropionate

mGluRs:

metabotropic glutamate receptors

P-THEO:

8-phenyltheophylline

(rs)M-CPG:

(rs)-alpha-methyl-4-carboxyphenyl-glycine

trans-ACPD:

trans-d,l-1-aminocyclopentane-1,3-dicarboxyho acid

Refereces

  1. Collingridge, G. L., and Lester, R. A. 1989. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol. Rev. 40:143–208.

    Google Scholar 

  2. Mayer, M. L., and Miller, R. J. 1990. Excitatory aminoacid receptors, 2nd messengers and regulation of intracellular Ca2+ in mammalian neurons. Trends Pharmacol. Sci. 11:254–260.

    Google Scholar 

  3. Gasic, G. P., and Hollman, M. 1992. Molecular neurobiology of glutamate receptors. Annu. Rev. Physiol. 54:507–536.

    Google Scholar 

  4. 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 

  5. Holmann, M., and Heinemann, S. 1994. Cloned glutamate receptors. Annu. Rev. Neurosci. 17:31–108.

    Google Scholar 

  6. Gomez-Barriocanal, J., Barat, A., and Ramirez, G. 1982. Kainic acid binding sites in the developing chick optic tectum. Neurochem. Int. 4:157–166.

    Google Scholar 

  7. Henley, J. M., Moratello, R., Hung, S. P., and Barnard, E. A. 1989. Localization and quantitative autoradiography of glutamatergic ligand binding sites in chick brain. Eur. J. Neurosci. 1:516–523.

    Google Scholar 

  8. 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.

    Google Scholar 

  9. Henke, H., Schenker, T. M., and Cuenod, M. 1976. Uptake of neurotransmitter candidates by pigeon optic tectum. J. Neurochem. 26:125–130.

    Google Scholar 

  10. Ventura, a. L. M., and Paes de Carvalho, R. 1987. Development of adenosine-dependent cyclic AMP accumulation in the avian optic tectum. Develop. Brain Res. 35:141–147.

    Google Scholar 

  11. 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. Developm Neurosci. in press

  12. Williams, M. 1987. Purine receptors in mammalian tissues: pharmacology and functional significance. Ann. Rev. Pharmacol. Toxicol. 27:315–345.

    Google Scholar 

  13. Van Calker, D., Muller, M., and Hamprecht, B. 1979. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J. Neurochem. 33:999–1005.

    Google Scholar 

  14. Birbaunmer, L., Abramowitz, J., and Brown, A. M. 1990. Receptor-effector coupling by G proteins. Biochem. et Biophys. Acta 1031:163–224.

    Google Scholar 

  15. Olah, M. E., and Stilles, G. L. 1992. Adenosine receptors. Annu. Rev. Physiol. 54:211–225.

    Google Scholar 

  16. Marangos, P. J., Patel, J., Martino, A. M., Dilli, M., and Boulenger, J. P. 1983. Differential binding properties of adenosine receptor agonists and antagonists in brain. J. Neurochem. 41:367–374.

    Google Scholar 

  17. Cotman, C. W., Kahle, J. S., Miller, S. E., Ulas, J., and Bridges, R. J. 1995. Excitatory amino acid neurotransmission. Pages 75–85,in Bloom, F. E., and Kuppfer, D. J. (eds), Psychopharmacology. The fourth generation of progress, Raven Press, New York.

    Google Scholar 

  18. Pin, J. P., and Duvoisin, R. 1995. Reviews: neurotransmitter receptors. I. The metabotropic glutamate receptors: structure and functions. Neuropharmacol. 34:1–26.

    Google Scholar 

  19. Schoepp, D. D., and Conn, P. J. 1993. Metabotropic glutamate receptors in brain function and pathology. Trends in Pharmacol. Sci. 14:13–20.

    Google Scholar 

  20. Schoepp, D. D., Johnson, B. G., and Monn, J. A. 1992. Inhibition of cyclic AMP formation by a selective metabotropic glutamate receptor agonist. J. Neurochem. 58:1184–1186.

    Google Scholar 

  21. Schoepp, D. D., and Johnson, B. G. 1993a. Pharmacology of metabotropic glutamate receptor inhibition of cyclic AMP formation in the adult rat hippocampus. Neurochem. Int. 22:277–283.

    Google Scholar 

  22. Baba, A., Nishiuchi, Y., Uemura, A., and Iwata, H. 1988. Mechanism of excitatory amino acid-induced accumulation of cyclic AMP in hippocampal slices: role of extracellular chloride. J. Pharmacol. Exper. Therap. 245:299–304.

    Google Scholar 

  23. Winder, D. G., and Conr, P. J. 1992. Activation of metabotropic glutamate receptors in the hippocampus increases cyclic AMP accumulation. J. Neurochem. 59:375–378.

    Google Scholar 

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

    Google Scholar 

  25. Aramori, I., and Nakanishi, S. 1992. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 8:757–765.

    Google Scholar 

  26. 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.

    Google Scholar 

  27. Baba, A., Lee, E., Tatsuno, T., and Iwata, H. 1982. Cysteine sulfinic acid in the central nervous system: antagonistic effect of taurine on cysteine sulfinic acid-stimulated formation of cyclic AMP in guinea pig hippocampal slices. J. Neurochem. 38:1280–1285.

    Google Scholar 

  28. Rall, T. W., and Lehne, R. A. 1987. Ontogeny of adenosine 3′, 5′-monophosphate metabolism in guinea pig cerebral cortex. II. Development of responses to L-glutamate in the presence of adenosine or histamine. Molec. Cell. Biochem. 73:157–168.

    Google Scholar 

  29. Smellie, F. W., Davis, C. W., Daly, J. W., and Wells, J. N. 1979. Alkylxanthines: inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activity. Life Sciences 24:2475–2482.

    Google Scholar 

  30. Daly, J. W., Bruns, R. F., and Snyder, S. H. 1981. Adenosine receptors in the central nervous system relationship to the central actions of methylxanthines. Life Sciences 28:2083–2097.

    Google Scholar 

  31. Choi, D. W. 1988. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634.

    Google Scholar 

  32. Lipton, S. A., and Rosenberg, P. A. 1994. Excitatory amino acids as a final common pathway for neurological disorders. (Mechanisms of disease. Ed. Epstein, F. H.), New England J. Med. 330: 613–622.

    Google Scholar 

  33. Shimizu, H., Ichishita, H., and Odagiri, H. 1974. Stimulated formation of cyclic adenosine 3′,5′-monophosphate by aspartate and glutamate in cerebral cortical slices of guinea pig. J. Biol. Chem. 249:5955–5962.

    Google Scholar 

  34. Bruns, R. F., Pons, F., and Daly, J. W. 1980. Glutamate- and veratridine-elicited accumulations of cyclic AMP in brain slices: a role for factors which potentiate adenosine-responsive systems. Brain Res. 189:550–555.

    Google Scholar 

  35. Shonk, R. F., Binder, B., and Rall, T. W. 1987. Ontogeny of adenosine 3′,5′-monophosphate metabolism in rabbit cerebral cortex. Development of responses to histamine, norepinephrine, adenosine and glutamate. Molec. Cell. Biochem. 73:169–178.

    Google Scholar 

  36. Casabona, G., Genazzani, A. A., Di Stefano, M., Sortino, M. A., and Nicolleti, F. 1992. Developmental changes in the modulation of cyclic AMP formation by the metabotropic glutamate receptor agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid in brain slices. J. Neurochem. 59:1161–1163.

    Google Scholar 

  37. Littman, L., Munir, M., Flagg, S. D., and Robinson, M. B. 1992. Multiple mechanisms for inhibition of excitatory amino acid receptors coupled to phosphoinositide hydrolysis. J. Neurochem. 59: 1893–1904.

    Google Scholar 

  38. DeLapp, N. W., and Eckols, K. 1992. Forskolin stimulation of cyclic AMP accumulation in rat brain cortex slices is markedly enhanced by endogenous adenosine. J. Neurochem. 58:237–242.

    Google Scholar 

  39. Ascher, P., and Nowak, L. 1988. Quisqualate- and kainate-activated channels in mouse central neurones in culture. J. Physiol. 399:227–245.

    Google Scholar 

  40. Nicholson, C. D., Challiss, R. A., and Shahid, M. 1991. Differential modulation of tissue and therapeutic potential of selective inhibitors of cyclic nucleotide phosphodiesterase enzyme. Trends in Pharmacol. Scienc. 12:19–27.

    Google Scholar 

  41. Gustovsky, F., and Gutkind, J. S. 1991. Selective effects of activation of protein kinase C isozymes on cyclic AMP accumulation. Mol. Pharmacol. 139:124–129.

    Google Scholar 

  42. Nakanishi, S. 1992. Molecular diversity of glutamate receptors and implications for brain function. Science 258:597–603.

    Google Scholar 

  43. Cartmell, J., Kemp, J. A., Alexander, S. P. H., and Kendall, D. A. 1993. Inhibition of A2b adenosine receptor-elicited and forskolin-stimulated cyclic AMP accumulation by L-2-amino-4-phosphonbutyrate (L-AP4). Br. J. Pharmacol. 108:268P.

    Google Scholar 

  44. Okamoto, N., Hori, S., Akazawa, C., Hayashi, Y., Shigemoto, R., Mizuno, N., and Nakanishi, S. 1994. Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction. J. Biol. Chem. 269: 1231–1236.

    Google Scholar 

  45. 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 potencials. Molec. Pharmacol. 41:337–345.

    Google Scholar 

  46. Eaton, S. A., Jane, D. E., Jones, P. L. St J., Porter, R. H. P., Pook, P. C.-K., Sunter, D. C., Udvarhelyi, P. M., Roberts, P. J., Salt, T. E., and Watkins, J. C. 1993. Competitive antagonism at metabotropic glutamate receptors by (S)-4-carboxyphenylglycine and (RS)-alpha-methyl-4-carboxyphe nylglycine. Eur. J. Pharmacol. 244:195–197.

    Google Scholar 

  47. Kemp, M., Roberts, P., Pook, P., Jane, D., Jones, A., Jones, P., Sunter, D., Udvarhelyi, P., and Watkins, J. 1994. Antagonism of presynaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors. Eur. J. Pharmacol. 266: 187–192.

    Google Scholar 

  48. Watkins, J., and Collingridge, G. 1994. Phenylglycine derivatives as antagonists of metabotropic glutamate receptors. TIPS 15:333–342.

    Google Scholar 

  49. Birse, E. F., Eaton, S. A., Jane, D. E., Jones, P. L. St J., Porter, R. H. P., Pook, P. C.-K., Sunter, D. C., Udvarhelyi, P. M., Wharton, B., Roberts, P. J., Salt, T. E., and Watkins, J. C. 1993. Phenyglycine derivatives as new pharmacological tools for investigating the role of metabotropic glutamate receptors in the central nervous system. Neurosci. 52:481–488.

    Google Scholar 

  50. Lonart, G., Alagarsamy, S., Ravula, R., Wang, J., and Johnson, K. M. 1992. Inhibition of the phospholipase C-linked metabotropic glutamate receptor by 2-amino-3-phosphonopropionate is dependent on extracellular calcium. J. Neurochem. 59:772–775.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tasca, C.I., Vendite, D., Martini, L.H. et al. Modulation of adenosine-induced cAMP accumulation via metabotropic glutamate receptors in chick optic tectum. Neurochem Res 20, 1033–1039 (1995). https://doi.org/10.1007/BF00995557

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00995557

Key Words

Navigation