Skip to main content

Advertisement

Log in

In vivo Quinolinic Acid Increases Synaptosomal Glutamate Release in Rats: Reversal by Guanosine

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Glutamate, the main excitatory neurotransmitter in the mammalian central nervous system (CNS), plays important role in brain physiological and pathological events. Quinolinic acid (QA) is a glutamatergic agent that induces seizures and is involved in the etiology of epilepsy. Guanine-based purines (GBPs) (guanosine and GMP) have been shown to exert neuroprotective effects against glutamatergic excitotoxic events. In this study, the influence of QA and GBPs on synaptosomal glutamate release and uptake in rats was investigated. We had previously demonstrated that QA “in vitro” stimulates synaptosomal L-[3H]glutamate release. In this work, we show that i.c.v. QA administration induced seizures in rats and was able to stimulate synaptosomal L-[3H]glutamate release. This in vivo neurochemical effect was prevented by i.p. guanosine only when this nucleoside prevented QA-induced seizures. I.c.v. QA did not affect synaptosomal L-[3H]glutamate uptake. These data provided new evidence on the role of QA and GBPs on glutamatergic system in rat brain.

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

References

  1. I. P. Lapin (1978) ArticleTitleStimulant and convulsant effects of kynurenines injected into brain ventricles in mice J. Neural Trans 42 37–43 Occurrence Handle1:CAS:528:DyaE1cXktVWjt7g%3D

    CAS  Google Scholar 

  2. R. G. Tavares C. I. Tasca C.E.S. Santos M. Wajner D. O. Souza C. S. Dutra-Filho (2000) ArticleTitleQuinolinic acid inhibits glutamate uptake into synaptic vesicles from rat brain NeuroReport 11 249–253 Occurrence Handle1:CAS:528:DC%2BD3cXhtVWhuro%3D Occurrence Handle10674464

    CAS  PubMed  Google Scholar 

  3. R. G. Tavares C. I. Tasca C. E. Santos L. B. Alves L. O. Porciúncula T. Emanuelli D. O. Souza (2002) ArticleTitleQuinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes Neurochem. Int 40 621–627 Occurrence Handle1:CAS:528:DC%2BD38XitFWiu7s%3D Occurrence Handle11900857

    CAS  PubMed  Google Scholar 

  4. T. W. Stone (2001) ArticleTitleKynurenic acid antagonists and kynurenine pathway inhibitors Expert Opin Investig Drugs 10 633–645 Occurrence Handle1:CAS:528:DC%2BD3MXis1Kjsrg%3D Occurrence Handle11281814

    CAS  PubMed  Google Scholar 

  5. N. J. Allen R. Karadottir D. Attwell (2004) ArticleTitleReversal or reduction of glutamate and GABA transport in CNS pathology and therapy Pflugers Arch 449 132–142 Occurrence Handle1:CAS:528:DC%2BD2cXhtVejurvM Occurrence Handle15338308

    CAS  PubMed  Google Scholar 

  6. N. J. Maragakis J. D. Rothstein (2004) ArticleTitleGlutamate transporters: animal models to neurologic disease Neurobiol Dis 15 461–473 Occurrence Handle1:CAS:528:DC%2BD2cXivVKnu74%3D Occurrence Handle15056453

    CAS  PubMed  Google Scholar 

  7. S. Ozawa H. Kamiya K. Tsukuki (1998) ArticleTitleGlutamate receptors in the mammalian central nervous system Prog. Neurobiol 54 581–618 Occurrence Handle1:CAS:528:DyaK1cXitlymt7w%3D Occurrence Handle9550192

    CAS  PubMed  Google Scholar 

  8. N. C. Danbolt (2001) ArticleTitleThe high affinity uptake system for excitatory amino acids in the brain Prog. Neurobiol 44 377–396

    Google Scholar 

  9. Y. Chen R. A. Swanson (2003) ArticleTitleAstrocyte and brain injury J. Cerebr. Blood F. Metab 23 137–149

    Google Scholar 

  10. M. B. Robinson L. A. Dowd (1997) ArticleTitleHeterogeneity and functional subtypes of sodium-dependent glutamate transporters in the mammalian central nervous system Adv. Pharmacol 37 69–115 Occurrence Handle1:CAS:528:DyaK2sXivVOhsA%3D%3D Occurrence Handle8891100

    CAS  PubMed  Google Scholar 

  11. C. M. Anderson R. A. Swanson (2000) ArticleTitleAstrocyte glutamate transport: review of properties, regulation and physiological functions Glia 32 1–14 Occurrence Handle1:STN:280:DC%2BD3M%2FivVGmtA%3D%3D Occurrence Handle10975906

    CAS  PubMed  Google Scholar 

  12. E. M. Fykse F. Fonnum (1996) ArticleTitleAmino acid neurotransmission: dynamics of vesicular uptake Neurochem. Res 21 1053–1060 Occurrence Handle1:CAS:528:DyaK28Xmt12gsrw%3D Occurrence Handle8897468

    CAS  PubMed  Google Scholar 

  13. H. Wolosker D. O. Souza L. Meis Particlede (1996) ArticleTitleRegulation of glutamate transport into synaptic vesicles by chloride and proton gradient J. Biol. Chem 271 11726–11731 Occurrence Handle1:CAS:528:DyaK28XjtV2ltb0%3D Occurrence Handle8662610

    CAS  PubMed  Google Scholar 

  14. M. P. Rathbone P. J. Middlemiss J. W. Gysbergs C. Andrew M.A.R. Herma J. K. Ree R. Ciccarelli P. Di Iorio F. Caciagli (1999) ArticleTitleTrophic effects of purines in neurons and glial cells Prog. Neurobiol 59 663–690 Occurrence Handle1:CAS:528:DyaK1MXmslyksLs%3D Occurrence Handle10845757

    CAS  PubMed  Google Scholar 

  15. B. M. Baron M. W. Dudley D. R. McCarty F. P. Miller I. J. Reynolds C. J. Schmidt (1989) ArticleTitleGuanine 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 Occurrence Handle1:CAS:528:DyaL1MXkvFWjsL8%3D Occurrence Handle2545857

    CAS  PubMed  Google Scholar 

  16. M. M. Paz M. Ramos G. Ramirez D. O. Souza (1994) ArticleTitleDifferential effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity in chick optic tectum FEBS Lett 355 205–208 Occurrence Handle1:STN:280:ByqD2szltlA%3D Occurrence Handle7982502

    CAS  PubMed  Google Scholar 

  17. J. S. Burgos A. Barat D. O. Souza G Ramírez (1998) ArticleTitleGuanine nucleotides protect against kainate toxicity in an ex vivo chick retinal preparation FEBS Lett 430 176–180 Occurrence Handle1:CAS:528:DyaK1cXkt1yht7w%3D Occurrence Handle9688533

    CAS  PubMed  Google Scholar 

  18. M. A. Rubin A. C. Medeiros P. C. Rocha C. B. Livi G. Ramirez D. O. Souza (1997) ArticleTitleEffect of guanine nucleotides on [3H]glutamate binding and on adenylate cyclase activity in rat brain membranes Neurochem. Res 22 181–187 Occurrence Handle1:CAS:528:DyaK2sXjtVOis78%3D Occurrence Handle9016844

    CAS  PubMed  Google Scholar 

  19. M.E.S. Frizzo D. R. Lara K.C.S. Dahm A. S. Prokopiuk R. Swanson D. O. Souza (2001) ArticleTitleActivation of glutamate uptake by guanosine in primary astrocyte cultures NeuroReport 12 879–881 Occurrence Handle1:CAS:528:DC%2BD3MXisVygt78%3D Occurrence Handle11277601

    CAS  PubMed  Google Scholar 

  20. M. E. S. Frizzo D. R. Lara A. S. Prokopiuk C. R. Vargas C. G. Salbego M. Wajner D. O. Souza (2002) ArticleTitleGuanosine enhances glutamate uptake in brain cortical slices at normal and excitotoxic conditions Cell. Mol. Neurobiol 22 353–363 Occurrence Handle1:CAS:528:DC%2BD38XnvFOhsr0%3D Occurrence Handle12469876

    CAS  PubMed  Google Scholar 

  21. M.E.S. Frizzo F. A. Soares L. P. Dall’Onder D. R. Lara R. A. Swanson D. O. Souza (2003) ArticleTitleExtracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake Brain Res 972 84–89 Occurrence Handle1:CAS:528:DC%2BD3sXjtVCqu7s%3D Occurrence Handle12711081

    CAS  PubMed  Google Scholar 

  22. A. P. Schmidt D. R. Lara J. F. Maraschin A. S. Perla D. O. Souza (2000) ArticleTitleGuanosine and GMP prevent seizures induced by quinolinic acid in mice Brain Res 864 40–43 Occurrence Handle1:CAS:528:DC%2BD3cXivVGhtr0%3D Occurrence Handle10793184

    CAS  PubMed  Google Scholar 

  23. D. R. Lara A. P. Schmidt M.E.S. Frizzo J. S. Burgos G. Ramirez D. O. Souza (2001) ArticleTitleEffect of orally administered guanosine on seizures and death induced by glutamatergic agents Brain Res 912 176–180 Occurrence Handle1:CAS:528:DC%2BD3MXmsFahsLc%3D Occurrence Handle11532434

    CAS  PubMed  Google Scholar 

  24. F. A. Soares A. P. Schmidt M. Farina M. E. Frizzo R. G. Tavares L. V. Portela D. R. Lara D. O. Souza (2004) ArticleTitleAnticonvulsant effect of GMP depends on its conversion to guanosine Brain Res 1005 182–186 Occurrence Handle1:CAS:528:DC%2BD2cXisVGns78%3D Occurrence Handle15044076

    CAS  PubMed  Google Scholar 

  25. E. R. Vinadé A. P. Schmidt M.E.S. Frizzo I. Izquierdo E. Elizabetsky D. O. Souza (2003) ArticleTitleChronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice Brain Res 977 97–102 Occurrence Handle12788518

    PubMed  Google Scholar 

  26. E. R. Vinadé A. P. Schmidt M.E.S. Frizzo L. V. Portela F. A. Soares F. D. Schwalm E. Elisabetsky I. Izquierdo D. O. Souza (2005) ArticleTitleEffects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats Journal of Neurosci. Res 79 248–253

    Google Scholar 

  27. E. R. Vinade I. Izquierdo D. R. Lara A. P. Schmidt D. O. Souza (2004) ArticleTitleOral administration of guanosine impairs inhibitory avoidance performance in rats and mice Neurobiol. Learn. Mem 81 137–143 Occurrence Handle1:CAS:528:DC%2BD2cXhsFWlu70%3D Occurrence Handle14990233

    CAS  PubMed  Google Scholar 

  28. P. R. Dunkley J. W. Heath S. M. Harrison P. E. Jarvie P. J. Glenfield J. A. Rostas (1988) ArticleTitleA rapid Percoll gradient procedure for isolation of synaptosomes directly from an S1 fration: homogeneity and morphology of subcellular fractions Brain Res 441 59–71

    Google Scholar 

  29. A. K. Nagi T. A. Shuster A. V. Delgado-Escueta (1986) ArticleTitleEcto-ATPase of mammalian synaptossomes: identification and enzymic characterization J. Neurochem 47 976–986 Occurrence Handle2942643

    PubMed  Google Scholar 

  30. O. H. Lowry N. J. Rosebrough A. L. Farr R. J. Randall (1951) ArticleTitleProtein measurement with the Folin phenol reagent J. Biol. Chem 193 65–275

    Google Scholar 

  31. P. V. Migues R. B. Leal M. Mantovani M. Nicolau N. H. Gabilan (1999) ArticleTitleSynaptosomal glutamate release induced by the fraction Bc2 from the venom of the sea anemone Bunodosoma caissarum NeuroReport 10 67–70 Occurrence Handle1:CAS:528:DyaK1MXjtVWrurY%3D Occurrence Handle10094135

    CAS  PubMed  Google Scholar 

  32. S. M. Sequeira J. O. Malva A. P. Carvalho C. M. Carvalho (2001) ArticleTitlePresynaptic N-methyl-D-aspartate receptor activation inhibits neurotransmitter release through nitric oxide formation in rat hippocampal nerve terminals Mol. Brain Res 89 111–118 Occurrence Handle1:CAS:528:DC%2BD3MXislGksbc%3D Occurrence Handle11311981

    CAS  PubMed  Google Scholar 

  33. D. L. Oliveira J. F. Horn J. M. Rodrigues M.E.S. Frizzo E. Moriguchi D. O. Souza S. Wofchuk (2004) ArticleTitleQuinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine Brain Res 1018 48–54 Occurrence Handle15262204

    PubMed  Google Scholar 

  34. Tavares R.G., Schmidt A.P., Tasca C.I., and Souza D.O. In vivo administration of quinolinic acid stimulates glutamate uptake in synaptic vesicles from rat brain: an effect prevented by guanine-based purines. Submitted to Brain Research

  35. D. G. Bole K. Hirata T. Ueda (2002) ArticleTitleProlonged depolarization of rat cerebral synaptosomes leads to an increase in vesicular glutamate content Neurosci Lett 322 17–20 Occurrence Handle1:CAS:528:DC%2BD38XhslWhsL4%3D Occurrence Handle11958833

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Diogo O. Souza.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tavares, R.G., Schmidt, A.P., Abud, J. et al. In vivo Quinolinic Acid Increases Synaptosomal Glutamate Release in Rats: Reversal by Guanosine. Neurochem Res 30, 439–444 (2005). https://doi.org/10.1007/s11064-005-2678-0

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-005-2678-0

Keywords

Navigation