Attenuation of Excitatory Amino Acid Toxicity by Metabotropic Glutamate Receptor Agonists and Aniracetam in Primary Cultures of Cerebellar Granule Cells
Version of Record online: 5 OCT 2006
Journal of Neurochemistry
Volume 61, Issue 2, pages 683–689, August 1993
How to Cite
Pizzi, M., Fallacara, C., Arrighi, V., Memo, M. and Spano, P. (1993), Attenuation of Excitatory Amino Acid Toxicity by Metabotropic Glutamate Receptor Agonists and Aniracetam in Primary Cultures of Cerebellar Granule Cells. Journal of Neurochemistry, 61: 683–689. doi: 10.1111/j.1471-4159.1993.tb02173.x
- Issue online: 5 OCT 2006
- Version of Record online: 5 OCT 2006
- Received August 11, 1992; revised January 4, 1993; accepted January 5, 1993.
- Metabotropic receptor;
Abstract: Activation of glutamate ionotropic receptors represents the primary event in the neurotoxicity process triggered by excitatory amino acids. We demonstrate here that the concentration-dependent stimulation of metabotropic glutamate receptor (mGluR) by the selective agonist trans-1-aminocyclopentane-1, 3-dicarboxylate or by quisqualate counteracts both glutamate- and kainate-induced neurotoxicity in primary cultures of rat cerebellar granule cells. The mGluR-evoked responses are potentiated by aniracetam, which per se also elicits neuroprotection. Aniracetam concentration-dependently counteracted glutsmate-, kainate-, or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced cell death and greatly facilitated neuroprotective response achieved by different concentrations of both quisqualate and trans-1-aminocyclopentane-1, 3-dicarboxylate. In addition, aniracetam potentiated the mGluR-coupled stimulation of phospholipase C, as revealed by the measurement of 3H-inositol phosphate formation. Thus, mGluRs could be a suitable target for novel pharmacological strategies pointing to the treatment of neurodegenerative diseases.