title: Attenuation of excitatory amino acid toxicity by metabotropic glutamate receptor agonists and aniracetam in primary cultures of cerebellar granule cells.
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 glutamate-, kainate-, or alpha-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.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, University of Brescia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pizzi
authors.forename: C
authors.initials: C
authors.lastname: Fallacara
authors.forename: V
authors.initials: V
authors.lastname: Arrighi
authors.forename: M
authors.initials: M
authors.lastname: Memo
authors.forename: P F
authors.initials: PF
authors.lastname: Spano
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D007295:Inositol Phosphates / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D011760:Pyrrolidinones / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*
chemical_list: D005971:Glutamates; D007295:Inositol Phosphates; D011760:Pyrrolidinones; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; C036466:aniracetam; D016318:Quisqualic Acid; D000242:Cyclic AMP; D007608:Kainic Acid