Abstract
1. The effect of guanosine on L-[2,3-3H]glutamate uptake was investigated in brain cortical slices under normal or oxygen–glucose deprivation (OGD) conditions.
2. In slices exposed to physiological conditions, guanosine (1–100 μM) stimulated glutamate uptake (up to 100%) in a concentration-dependent manner when a high (100 μM) but not a low (1 μM) concentration of glutamate was used.
3. In slices submitted to OGD, guanosine 1 and 100 μM also increased 100 μM glutamate uptake (38 and 70%, respectively).
4. The increasing of glutamate and taurine released to the incubation medium in cortical slices submitted to OGD were significantly attenuated by the presence of guanosine in the incubation medium.
5. Guanosine prevented the increase in propidium iodide incorporation into cortical slices induced by OGD, indicating a protective role against ischemic injury.
6. These results support the hypothesis of a protective role for guanosine during brain ischemia, possibly by activating glutamate uptake into neural cells.
This is a preview of subscription content, log in via an institution to check access.
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 32:1–14.
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.
Boldyrev, A. A., Johnson, P., Wei, Y., Tan, Y., and Carpenter, D. O. (1999). Carnosine and taurine protect rat cerebellar granular cells from free radical damage. Neurosci. Lett. 263:169–172.
Ciccarelli, R., Di Iorio, P., Giuliani, P., D'Alimonte, I., Ballerini, P., Caciagli, F., and Rathbone, M. (1999). Rat cultured astrocytes release guanine-based purines in basal conditions and after hypoxia/ hypoglycemia. Glia 25:93–98.
Danbolt, N. C. (2001). Glutamate uptake. Prog. Neurobiol. 65:1–105.
Dirnagl, U., Iadecola, C., and Moskowitz, M. A. (1999). Pathobiology of ischemic stroke: An integrated view. Trends Neurosci. 22:391–397.
Dobolyi, ´ A., Reichart, A., Szikra, T., Nyitrai, G., K´ ekesi, K. A., and Juh´ asz, G. (2000). Sustained depolarization induces changes in the extracellular concentrations of purine and pyrimidine nucleosides in the rat thalamus. Neurochem. Int. 37:71–79.
Duan, S., 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.
Frizzo, M. E. S., Lara, D. R., Dahm, K. C., 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.
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.
Greene, J. G., and Greenamyre, J. T. (1996). Bioenergetics and glutamate excitotoxicity. Prog. Neurobiol. 48:613–634.
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.
Joseph, M. H., and Marsden, C. A. (1986). Amino acids and small peptides. In Lim, C. K. (ed.), HPLC of Small Peptides, IRL Press, Oxford, pp. 13–27.
Jurkowitz, M. S., Litsky, M. L., and Browning, M. J. (1998). Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitocondrial inhibition: Correlation between protection and ATP preservation. J. Neurochem. 71:535–548.
Lara, D. R., Schmidt, A. P., Frizzo, M. E. S., Burgos, J. S., Ramirez, G., and Souza, D. O. (2001). Effect of orally administered guanosine on seizures and death induced by glutamatergic agents. Brain Res. 912:176–180.
Lee, J. M., Zipfel, G. J., and Choi, D.W. (1999). The changing landscape of ischaemic brain injury mechanisms. Nature 399:A7–A14.
Masliah, E., Raber, J., Alford, M., Mallory, M., Mattson, M. P., Yang, D., Wong, D., and Mucke, L. (1998). Amyloid protein precursor stimulates excitatory amino acid transport. Implications for roles in neuroprotection and pathogenesis. J. Biol. Chem. 273:12548–12554.
Meldrum, B. S. (2000). Glutamate as a neurotransmitter in the brain: Review of physiology and pathology. J. Nutr. 130:1007S–1015S.
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.
Munir, M., Correale, D. M., and Robinson, M. B. (2000). Substrate-induced up-regulation of Na(C)-dependent glutamate transport activity. Neurochem. Int. 37:147–162.
Nicholls, D. G., and Budd, S. L. (1998). Mitochondria and neuronal glutamate excitotoxicity. Biochem. Biophys. Acta 1366:97–112.
Nieoullon, A., Kerkerian, L., and Dusticier, N. (1983). Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum. Neurosci. Lett. 43:191–196.
Nishizawa, Y. (2001). Glutamate release and neuronal damage in ischemia. Life Sci. 69:369–381. vOzawa, S., Kamiya, H., and Tsuzuki, K. (1998). Glutamate receptors in the mammalian central nervous system. Prog. Neurobiol. 54:581–618.
Peterson, G. L. (1977). Review of the Folin phenol protein quantitation method of Lowry, Rosebrough, Farr and Randall. Anal. Biochem. 83:346–356.
Phillis, J. W., Ren, J., and O'Regan, M. H. (2000). Transporter reversal as a mechanism of glutamate release from the ischemic rat cerebral cortex: studies with DL-threo-beta-benzyloxyaspartate. Brain Res. 880:224.
Rathbone, M. P., Middlemiss, P. J., Gysbers, J. W., Andrew, C., Herman, M. A. R., Reed, J. K., Ciccarelli, R., Di Iorio, P., and Caciagli, F. (1999). Tropic effects of purines in neurons and glial cells. Prog. Neurobiol. 59:663–690.
Sanchez-Carbente, M. R., and Massieu, L. (1999). Transient inhibition of glutamate uptake in vivo induces neurodegeneration when energy metabolism is impaired. J. Neurochem. 72:129–138.
Saransaari, P., and Oja, S. S. (2000). Taurine and neural cell damage. Amino Acids 19:509–526.
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.
Segovia, G., Porras, A., Del Arco, A., and Mora, F. (2001). Glutamatergic neurotransmission in aging: A critical perspective. Mech. Ageing Dev. 122:1–29.
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.
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.
Stover, J. F., and Unterberg, A. W. (2000). Increased cerebrospinal fluid glutamate and taurine concentrations are associated with traumatic brain edema formation in rats. Brain Res. 875:51–55.
Tang, X. C., Rao, M. R., Hu, G., and Wang, H. (2000). Alterations of amino acid levels from striatum, hippocampus, and cerebral cortex induced by global cerebral ischemia in gerbil. Acta Pharmacol. Sin. 21:819–823.
Traversa, U., Bombi, G., Di Iorio, P., Ciccarelli, R., Werstiuk, E. S., and Rathbone, M. (2002). Specific [3H]-guanosine binding sites in rat brain membranes. Br. J. Pharmacol. 135:969–976.
Uemura, Y., Miller, J. M., Matson, W. R., and Beal, M. F. (1991). Neurochemical analysis of focal ischemia in rats. Stroke 22:1548–1553.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
dos Santos Frizzo, M.E., Lara, D.R., Prokopiuk, A.d. et al. Guanosine Enhances Glutamate Uptake in Brain Cortical Slices at Normal and Excitotoxic Conditions. Cell Mol Neurobiol 22, 353–363 (2002). https://doi.org/10.1023/A:1020728203682
Issue Date:
DOI: https://doi.org/10.1023/A:1020728203682