Skip to main content
SpringerLink
Log in

Guanosine Enhances Glutamate Transport Capacity in Brain Cortical Slices

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

  1. 1.

    The effect of guanosine on L-[3H] glutamate uptake was investigated in brain cortical slices within physio-pathological range of glutamate(1–1000 μ M). In these conditions, glutamate uptake was significantly enhanced in slices treated with 100 μ M guanosine only at 100 and 300 μ M glutamate (44 and 52%, respectively).

  2. 2.

    Evaluation of kinetic parameters showed that guanosine affected significantly only uptake Vmax (23%).

  3. 3.

    The guanosine withdrawal did not abolish its significant effect on glutamate uptake when 100 or 300 μ M glutamate were used (an increase of 66 and 35%, respectively).

  4. 4.

    These results support the hypothesis of a protective role for guanosine during excitotoxic conditions when glutamate levels are enhanced (e.g. brain ischemia and seizures), possibly by activating glutamate uptake. Moreover, our results may contribute to understand the antiexcitotoxic mechanism of guanosine on glutamate transport, giving new information concerning its mechanism of action.

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

  • Anderson, C. M., and Swanson, R. A. (2000). Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 32(1):1–14.

    Article  PubMed  Google Scholar 

  • Asai, S., Zhao, H., Yamashita, A., Jike, T., Kunimatsu, T., Nagata, T., Kohno, T., and Ishikawa, K. (1999). Nicergoline enhances glutamate re-uptake and protects against brain damage in rat global brain ischemia. Eur. J. Pharmacol. 383:267–274.

    Article  PubMed  Google Scholar 

  • Brundege, J. M., and Dunwiddie, T. V. (1997). Role of adenosine as a modulator of synaptic activity in the central nervous system. Adv. Pharmacol. 39:353–391.

    PubMed  Google Scholar 

  • Ciccarelli, R., Di Iorio, P., Giuliani, P., D’Alimonte, I., Ballerini, P., Caciagli, F., and Rathbone, M. P. (1999). Rat cultured astrocytes release guanine-based purines in basal conditions and after hypoxia/hypoglycemia. Glia 25:93–98.

    Article  PubMed  Google Scholar 

  • Danbolt, N. C. (2001). Glutamate uptake. Prog. Neurobiol. 65:1–105.

    Article  PubMed  Google Scholar 

  • Dobolyi, Á., Reichart, A., Szikra, T., Nyitrai, G., Kékesi, K. A., and JuhÁsz, G. (2000). Sustained depolarization induces changes in the extracellular concentrations of purine and pyrimidine nucleosides in the rat thalamus. Neurochem. Int. 37:71–79.

    Article  PubMed  Google Scholar 

  • Duan, S. M., Anderson, C. M., Stein, B. A., and Swanson, R. A. (1999). Glutamate induces rapid upregulation of astrocyte glutamate transport and cell-surface expression of GLAST. J. Neurosci. 19:10193–10200.

    PubMed  Google Scholar 

  • Frizzo, M. E., Lara, D. R., Dahm, K. C. S., Prokopiuk, A. S., Swanson, R. A., and Souza, D. O. (2001). Activation of glutamate uptake by guanosine in primary astrocyte cultures. NeuroReport 12:879– 881.

    Article  PubMed  Google Scholar 

  • Frizzo, M. E., Lara, D. R., Prokopiuk, A. S., Vargas, C. R., Salbego, C. G., Wajner, M., and Souza, D. O. (2002). Guanosine enhances glutamate uptake in brain cortical slices at normal and excitotoxic conditions. Cell. Mol. Neurob. 22:353–363.

    Article  Google Scholar 

  • Frizzo, M. E., Soares, F. A., Dall’Onder, L. P., Lara, D. R., Swanson, R. A., and Souza, D. O. (2003). Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake. Brain Res. 972:84–89.

    Article  PubMed  Google Scholar 

  • Gegelashvili, G., Civenni, G., Racagni, G., Danbolt, N. C., Schousboe, I., and Schousboe, A. (1996). Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes. NeuroReport 8:261–265.

    PubMed  Google Scholar 

  • Greene, J. G., and Greenamyre, J. T. (1996). Bioenergetics and glutamate excitotoxicity. Prog. Neurobiol. 48:613–634.

    Article  PubMed  Google Scholar 

  • Izquierdo, I., Medina, J. H., Vianna, M. R., Izquierdo, L. A., and Barros, D. M. (1999). Separate mechanisms for short- and long-term memory. Behav. Brain Res. 103: 1–11.

    Article  PubMed  Google Scholar 

  • Lara, D. R., Schmidt, A. P., Frizzo, M. E., Burgos, J. S., Ramírez, G., and Souza, D. O. (2001). Effect of orally administered guanosine on seizures and death induced by glutamatergic agents. Brain Res. 912:176–180.

    Article  PubMed  Google Scholar 

  • Lee, J. M., Zipfel, G. J., and Choi, D. W. (1999). The changing landscape of ischaemic brain injury mechanisms. Nature 399:A7–A14.

    PubMed  Google Scholar 

  • Maragakis, N. J., and Rothstein, J. D. (2004). Glutamate transporters: Animal models to neurologic disease. Neurobiol. Dis. 15:461–473.

    Article  PubMed  Google Scholar 

  • Meldrum, B. S., Akbar, M. T., and Chapman, A. G. (1999). Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res. 36:189–204.

    Article  PubMed  Google Scholar 

  • Meldrum, B. S. (2000). Glutamate as a neurotransmitter in the brain: Review of physiology and pathology. J. Nutr. 130:1007S–1015S.

    PubMed  Google Scholar 

  • Munir, M., Correale, D. M., and Robinson, M. B. (2000). Substrate-induced up-regulation of Na+-dependent glutamate transport activity. Neurochem. Int. 37:147–162.

    Article  PubMed  Google Scholar 

  • Nishizawa, Y. (2001). Glutamate release and neuronal damage in ischemia. Life Sci. 69:369–381.

    Article  PubMed  Google Scholar 

  • Ozawa, S., Kamiya, H., and Tsuzuki, K. (1998). Glutamate receptors in the mammalian central nervous system. Prog. Neurobiol. 54:581–618.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Peterson, G. L.(1997). A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal. Biochem. 83:346–356.

    Article  Google Scholar 

  • Phillis, J. W., and O’Regan, M. H. (2003). Characterization of modes of release of amino acids in the ischemic/reperfused rat cerebral cortex. Neurochem. Int. 43: 461–467.

    Article  PubMed  Google Scholar 

  • Schmidt, A. P., Lara, D. R., Maraschin, J. F., Perla, A. S., and Souza, D. O. (2000). Guanosine and GMP prevent seizures induced by quinolinic acid in mice. Brain Res. 864:40–43.

    Article  PubMed  Google Scholar 

  • Schmidt, A. P., Ávila, T. T., and Souza, D. O. (2005). Intracerebroventricular guanine-based purines protect against seizures induced by quinolinic acid in mice. Neurochem. Res. 30:69–73.

    Article  PubMed  Google Scholar 

  • Segovia, G., Porras, A., Del Arco, A., and Mora, F. (2001). Glutamatergic neurotransmission in aging: A critical perspective. Mech. Ageing Dev. 122:1–29.

    Article  PubMed  Google Scholar 

  • Shimada, F., Shiga, Y., Morikawa, M., Kawazura, H., Morikawa, O., Matsuoka, T., Nishizaki, T., and Saito, N. (1999). The neuroprotective agent MS-153 stimulates glutamate uptake. Eur. J. Pharmacol. 386:263–270.

    Article  PubMed  Google Scholar 

  • Soares, F. A., Schmidt, A. P., Farina, M., Frizzo, M. E., Tavares, R. G., Portela, L. V., Lara, D. R., and Souza, D. O. (2004). Anticonvulsant effect of GMP depends on its conversion to guanosine. Brain Res. 1005:182–186.

    Article  PubMed  Google Scholar 

  • 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 

  • Vinadé, E. R., Schmidt, A. P., Frizzo, M. E., Izquierdo, I., Elisabetsky, E., and Souza, D. O. (2003). Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice. Brain Res. 977:97–102.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Bioquímica ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo), Porto Alegre, RS, 90035-003, Brazil

    Marcos Emílio Frizzo, Fábio Duarte Schwalm, Juliana Karl Frizzo, Félix Antunes Soares & Diogo Onofre Souza

  2. Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Marcos Emílio Frizzo

Authors
  1. Marcos Emílio Frizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fábio Duarte Schwalm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliana Karl Frizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Félix Antunes Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Diogo Onofre Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcos Emílio Frizzo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frizzo, M.E., Schwalm, F.D., Frizzo, J.K. et al. Guanosine Enhances Glutamate Transport Capacity in Brain Cortical Slices. Cell Mol Neurobiol 25, 913–921 (2005). https://doi.org/10.1007/s10571-005-4939-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-005-4939-5

Keywords

Search

Navigation