Abstract
In this study we show that the glutamate ionotropic agonist kainate (KA) stimulates the efflux of preloadedd-[3H]aspartate (D-[3H]Asp) and inhibits the uptake of this amino acid in cerebellar slices. The effect of this agonist on the efflux of D-[3H]Asp is sensitive to(i) 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2-3-dione (NBQX), indicating the involvement of KA/(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and is(ii) partially tetrodotoxin (TTX)-sensitive, indicating that pre-(TTX-insensitive) and post-synaptic (TTX-sensitive) KA/AMPA receptors are involved. In contrast, the effect on uptake is NBQX- and TTX-insensitive indicating a direct interaction with glutamate transporters. AMPA inhibited D-[3H]Asp uptake and had no effect on D-[3H]Asp efflux. In the same system, the uptake but not the efflux of D-[3H]Asp was affected by dihydrokainate (DHK). The DHK-induced uptake inhibition occurred in the presence of TTX. NBQX inhibited DHK-induced effect at 5 mM but not at 1 mM DHK concentrations.
Similar content being viewed by others
References
Ferkany, J. W., and Coyle, J. T. 1983. Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids. J. Pharmacol. Exp. Ther. 225:399–406.
Johnston, G. A. R., Kennedy, S. M. E., and Twitchin, B. 1978. Action of the neurotoxin Kainic acid on high affinity uptake of L-Glutamate acid in rat brain slices. J. Neurochem. 32:121–127.
Garthwaite, J., and Wilkin, G. P. 1982. Kainic acid receptors and neurotoxicity in adult and immature rat cerebellar slices. Neurosci. 7:2499–2514.
Drejer, J., Larsson, O. M., and Schousboe, A. 1983. Characterization of uptake and release processes for D- and L-Aspartate in primary cultures of astrocytes and cerebellar granule cells. Neurochem. Res. 8:231–243.
Nicholls, D., and Attwell, D. 1990. The release and uptake of excitatory amino acids. Trends Pharmacol. Sci. 11:462–468.
Seeburg, P. H. 1993. The molecular biology of mammalian glutamate receptor channels. Trends Pharmacol. Sci. 16:359–364.
Naito, S., and Ueda, T. 1985. Characterization of glutamate uptake into synaptic vesicles. J. Neurochem. 44:99–109.
Levi, G., and Gallo, V. 1986. Release studies related to the neurotransmitter role of glutamate in the cerebellum: An overview. Neurochem. Res. 11:1626–1942.
Belhage, B., Rehder, V., Hansen, G. H., Kater, S. B., and Schousboe, A. 1992.3H-D-Aspartate release from cerebellar granule neurons is differentially regulated by glutamate- and K+-stimulation. J. Neurosci. Res. 33:436–444.
Ferkany, J. W., and Coyle, J. T. 1983 Evoked release of aspartate and glutamate: disparities between prelabeling and direct measurement. Brain Res. 278:279–282.
Poli, A., Contestabile, A., Migani, P., Rossi, L., Rondelli, C., Virgili, M., Bissoli, R., and Barnabei, O. 1985. Kainic acid differentially affects the synaptosomal release of endogenous and exogenous amino acidic neurotransmitters. J. Neurochem. 45: 1677–1686.
Levi, G., Patrizio, M., and Gallo, V. 1991. Release of endogenous and newly synthetized glutamate and other amino acids induced by non-N-Methyl-D-Aspartate receptor activation in cerebellar granule cell cultures. J. Neurochem. 56:199–206.
Müller, T., Möller, T., Berger, T., Schnitzer, J., Kettenmann, H. 1992. Calcium entry through kainate receptors and resulting potassium-channel blockade in Bergmann glial cells. Science. 256: 1563–1566.
Pines, G., Danbolt, N. C., Bjørås, M., Zhang, Y., Bendahan, A., Eide, L., Hermann, K., Storm-Mathisen, J., Seeburg, E., and Kanner, B. I. 1992. Cloning and expression of a rat brain L-Glutamate transporter. Nature. 360:464–467.
Tanaka, K. 1993. Expression cloning of a rat glutamate transporter. Neurosci. Res. 16:149–153.
Kanai, Y., and Hediger, M. A. 1992. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature. 260:467–471.
Lehre, K. P., Levy, L. M., Ottersen, O. P., Storm-Mathisen, J., and Danbolt, N. C. 1995. Differential expression of two glial glutamate transporters in the rat brain: Quantitative and immunocytochemical observations. J. Neurosci. 15:1835–1853.
Rothstein, J. D., Martin, L., Levey, A. I., Dykes-Hoberg, M., Jin, L., Wu, D., Nash, N., Kuncl, R. W. 1994. Localization of neuronal and glial glutamate transporters. Neuron. 13:713–725.
Torp, R., Danbolt, N. C., Babaie, E., Bjørås, M., Seeburg, E., Storm-Mathisen, J., and Otterson, O. P. 1994. Differential expression of two glial glutamate transporters in the rat brain: An In situ hybridization study. Eur. J. Neurosci. 6:936–942.
Robinson, M. B., Sinor, J. D., Dowd, L. A., and Kerwin, J. F. Jr. 1993. Subtypes of sodium-dependent high-affinity L-[3H]Glutamate transport activity: Pahrmacological specificity and regulation by sodium and potassium. J. Neurochem. 60:167–179.
Garlin, A. B., Sinor, A. D., Sinor, J. D., Jee, S. H., Grinspan, J. B., Robinson, M. B. 1995. Pharmacology of sodium-dependent high-affinity L-[3H]Glutamate transport in glial cultures. J. Neurochem. 64:2572–2580.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bouazzaoui, M., Kannengieser, C., Procksch, O. et al. Kainic acid, AMPA, and dihydrokainic acid effect on uptake and efflux ofd-[3H]aspartic acid in cerebellar slices. Neurochem Res 21, 1527–1533 (1996). https://doi.org/10.1007/BF02533101
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02533101