Journal of Molecular Neuroscience

, Volume 3, Issue 1, pp 39–45 | Cite as

Effects of guanine nucleotides on kainic acid binding and on adenylate cyclase in chick optic tectum and cerebellum

  • Diogo Onofre Souza
  • Galo Ramírez


Adenylate cyclase activity and binding of neurotransmitters to some receptors can be modulated simultaneously by guanine nucleotides. Furthermore it has been shown, in different neurotransmitter systems, that the ability of GTP to inhibit agonist binding is related to the capacity of the transmitter to modulate adenylate cyclase activity. In the present report we show that in chick optic tectum and cerebellum the effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity can be dissociated. In lysed membrane preparations, GTP, GDP, and GMP, or their analogs, displace binding of kainic acid with the same efficiency, whereas only GTP stimulates adenylate cyclase. In vesicle preparations, all three nucleotides inhibit binding of kainic acid without modifying adenylate cyclase activity. The present results suggest that, if adenylate cyclase is indeed coupled to this particular type of excitatory amino acid receptor, the coupling mechanism would be probably different from those operating in other neurotransmitter systems and also that the displacement of kainic acid by GDP and GMP (and even perhaps by GTP) is not likely to depend on the interaction between the receptor and a Gs-protein-mediated effector system.


Adenylate Cyclase Cyclase Activity Excitatory Amino Acid Guanine Nucleotide Kainic Acid 
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  1. Albano, J.D.M., Barnes, G.D., Maudsley, D., Brown, B.L., Etkins, R.P. (1974). Factors affecting the saturation assay of cyclic AMP in biological systems. Anal. Biochem. 60:130–141PubMedCrossRefGoogle Scholar
  2. Asano, T., Ui, M., Ogasawara, N. (1985). Prevention of the agonist binding to 4-aminobutyric acid B receptors by guanine nucleotides and islet-activating protein, pertussis toxin, in bovine cerebral cortex. J. Biol. Chem. 260:12653–12658PubMedGoogle Scholar
  3. Baba, A., Nishiuchi, Y., Uemura, A., Iwata, H. (1988). Mechanisms of excitatory amino acid-induced accumulation of cyclic AMP in hippocampal slices: Role of extracellular chloride. J. Pharmacol. Exp. Ther. 245:299–304PubMedGoogle Scholar
  4. Birnbaumer, L., Codina, J., Mattera, R., Cerione, R.A., Hildebrandt, J.D., Sunyer, T., Rojas, F.J., Caron, M.G., Lefkovitz, R.J., Iyengar, R. (1985). Regulation of hormone receptors and adenylate cyclases by guanine nucleotide binding N proteins. Recent Progr. Horm. Res. 41:41–95PubMedGoogle Scholar
  5. Bruns, R.F., Pons, F., Daly, W. (1980). Glutamate- and veratridine-elicited accumulations of cyclic AMP in brain slices: A role for factors which potentiate adenosine-responsiveness systems. Brain Res. 189:550–555PubMedCrossRefGoogle Scholar
  6. Chang, R.S.L., Snyder, S.H. (1980). Histamine H1-receptor binding sites in guinea pig brain membranes: Regulation of agonist interactions by guanine nucleotides and cations. J. Neurochem. 34:916–922PubMedCrossRefGoogle Scholar
  7. Crowder, J.M., Croucher, M.J., Bradford, H.F., Collins, J.F. (1987). Excitatory amino acid receptors and depolarization-induced Ca2+ influx into hippocampal slices. J. Neurochem. 48:1917–1924PubMedCrossRefGoogle Scholar
  8. Daly, J.W., McNeal, E., Partington, C., Neuwirth, M., Creveling, C.R. (1980). Accumulations of cyclic AMP in adenine-labeled cell-free preparations from guinea pig cerebral cortex: Role of alpha-adrenergic and H1-histaminergic receptors. J. Neurochem. 35:326–337PubMedCrossRefGoogle Scholar
  9. Eckestein, F., Cassel, D., Lefkovitz, H., Lowe, M., Selinger, O.Z. (1979). Guanosine 5′-O-(2-thiodiphosphate), an inhibitor of adenylate cyclase stimulation by guanine nucleotides and fluoride ions. J. Biol. Chem. 254:9829–9834Google Scholar
  10. Foster, A., Fagg, G. (1984). Acidic amino acid binding sites in mammalian neuronal membranes: Their characteristics and relationship to synaptic receptors. Brain Res. Rev. 7:103–164CrossRefGoogle Scholar
  11. Foster, A.A., Fagg, G.E., Harris, E.W., Cotman, C.W. (1982). Regulation of glutamate receptors: Possible role of phosphatidylserine. Brain Res. 242:374–377PubMedCrossRefGoogle Scholar
  12. Garthwaite, J., Garthwaite, G. (1987). Cellular origins of cyclic GMP responses to excitatory amino acid receptor agonist in rat cerebellum in vitro. J. Neurochem. 48:29–39PubMedCrossRefGoogle Scholar
  13. Gilman, A.G. (1987). G-proteins: Transducers of receptor-generated signal. Annu. Rev. Biochem. 56:615–649PubMedCrossRefGoogle Scholar
  14. Grigoriadis, D., Seeman, P. (1985). Complete conversion of brain D2 dopamine receptors from the high to the low affinity state for dopamine agonists, using sodium ions and guanine nucleotide. J. Neurochem. 44:1493–1502CrossRefGoogle Scholar
  15. Haga, K., Haga, T., Ichiyama, A. (1986). Recontituition of the muscarinic acetylcholine receptor. Guanine nucleotide-sensitive high affinity binding of agonist to purified muscarinic receptors recontituted with GTP-binding proteins (G1 and Go). J. Biol. Chem. 261:10133–10140PubMedGoogle Scholar
  16. Hildebrandt, J.D., Birnbaumer, L. (1983). Inhibitory regulation of adenylyl cyclase in the absence of stimulatory regulation. Requirements and kinetics of guanine nucleotide-induced inhibition of the cyc-S49 adenylyl cyclase. J. Biol. Chem. 258:13141–13147PubMedGoogle Scholar
  17. Hoffman, B.B., Lefkovitz, R.J. (1980). Radioligand binding studies of adrenergic receptors: New insights into molecular and physiological regulation. Annu. Rev. Pharmacol. Toxicol. 20:581–608PubMedCrossRefGoogle Scholar
  18. Kimura, N., Shimada, N. (1983). GDP does not mediate but rather inhibits hormonal signal to adenylate cyclase. J. Biol. Chem. 258:2278–2283PubMedGoogle Scholar
  19. Levitzki, A. (1987). Coupling of β-adrenergic receptors to adenylate cyclase and the role of the GTP binding protein in signal transduction. In,Perspectives on Receptor Classification. J.W. Black, D.H. Jenkinson, V.B. Gerskowitch (eds). Alan R. Liss, New York, pp 87–94Google Scholar
  20. Limbird, L.E. (1981). Activation and attenuation of adenylate cyclase. The role of GTP-binding proteins as macromolecular messengers in receptor-cyclase coupling. Biochem. J. 195:1–13PubMedGoogle Scholar
  21. Lyon, R.A., Davis, K.H., Titeler, M. (1987).3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors. Mol. Pharmacol. 31:194–199PubMedGoogle Scholar
  22. Monahan, B., Hood, W.F., Michel, J., Compton, R.P. (1988). Effects of guanine nucleotides onN-methyl-d-aspartate receptor-ligand interactions. Mol. Pharmacol. 34:111–116PubMedGoogle Scholar
  23. Nicoletti, F., Wroblewski, J.T., Iadarola, B.L., Costa, E. (1986). Serine-O-phosphate, an endogenous metabolite, inhibits the stimulation of inositol phospholipid hydrolysis elicited by ibotenic acid in rat hippocampal slices. Neuropharmacology 25:335–338PubMedCrossRefGoogle Scholar
  24. Ramírez, G., Gómez-Barriocanal, J., Escudero, E., Fernández-Quero, S., Barat, A. (1981). Development of excitatory amino acid binding sites in the chick optic tectum.Amino Acid Neurotransmitters. F.V. De Feudis, P. Mandel (eds), Raven Press, New York, pp 467–474Google Scholar
  25. Selley, D.E., Tyler, C.B., Bidlack, J.M. (1988). Guanine nucleotide regulation of (125I)β-endorphin binding to rat brain membranes: Monovalent cation requirement. J. Neurochem. 50:1844–1850PubMedCrossRefGoogle Scholar
  26. Sharif, N.A., Roberts, P.J. (1981). Regulation of cerebellarl-[3H]glutamate binding: Influence of guanine nucleotides and Na+ ions. Biochem. Pharmacol. 30:3019–3022PubMedCrossRefGoogle Scholar
  27. Shimizu, H., Ichista, H., 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. 249:5955–5962PubMedGoogle Scholar
  28. Shonk, R.F., Binder, B., Rall, T.W. (1987). Ontogeny of adenosine 3′,5′-monophosphate metabolism in rabbit cerebral cortex. Development of responses to histamine, norepinephrine, adenosine, and glutamate. Mol. Cell Biochem. 73:169–178PubMedGoogle Scholar
  29. Stiles, G. (1988). Adenosine receptor-G protein coupling in bovine brain membranes: effects of guanine nucleotides, salt, and solubilization. J. Neurochem. 51:1592–1598PubMedCrossRefGoogle Scholar
  30. Stryer, L. (1986). G proteins: A family of signal transducers. Annu. Rev. Cell Biol. 2:391–419PubMedCrossRefGoogle Scholar
  31. Thomsen, W.S., Jacquez, J.A., Neubig, R.R. (1988). Inhibition of adenylate cyclase is mediated by the high affinity conformation of the alpha 2-adrenergic receptor. Mol. Pharmacol. 34:814–822PubMedGoogle Scholar
  32. Tovey, K.C., Oldham, K.G., Whelan, J.A.M. (1974). A simple direct assay for cyclic AMP in plasma and other biological samples using an improved competitive protein binding technique. Clin. Chim. Acta 56:221–234PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser 1991

Authors and Affiliations

  • Diogo Onofre Souza
    • 1
  • Galo Ramírez
    • 2
  1. 1.Departamento de BioquímicaInstituto de Biociências, UFRGSPorto Alegre, RSBrasil
  2. 2.Centro de Biología Molecular (CSIC-UAM)Universidad Autónoma, CantoblancoMadridSpain

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