Activation of metabotropic glutamate receptors protects cultured neurons against apoptosis induced by β-amyloid peptide

A. Copani, V. Bruno, G. Battaglia, G. Leanza, R. Pellitteri, A. Russo, S. Stanzani, F. Nicoletti

Research output: Contribution to journalArticlepeer-review

Abstract

Prolonged exposure of cultured cortical cells or cultured cerebellar granule cells to the residue 25-35 fragment of β-amyloid peptide (βAP), βAP((25-35)), induced neuronal apoptosis, as revealed by morphological analysis, fluorescent chromatin staining, and immunodetection of oligonucleosomes released from the nucleus into the cytoplasm. βAP((25- 35))-induced apoptosis was insensitive to ionotropic glutamate receptor antagonists but was substantially attenuated by the metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid. The neuroprotective action of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid was antagonized by (RS)-α-methyl-4-carboxyphenylglycine and was mimicked by (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (a selective agonist of mGluR2 and -3 subtypes) and by L-2-amino-4-phosphobutanoate and L- serine-O-phosphate (selective agonists of mGluR4, -6, and -7 subtypes). However, whereas all of these drugs behaved as neuroprotectants in cultured cortical cells, only L-2-amino-4-phosphobutanoate and L-serine-O-phosphate [and not (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine] reduced βAP((25-35))-induced apoptosis in cultured cerebellar granule cells. The neuroprotective activity of mGluR agonists may be related to their ability to inhibit membrane Ca2+ conductance, because drugs that block voltage- sensitive Ca2+ channels, such as nimodipine or Co2+, could also attenuate βAP((25-35))-induced apoptosis.

Original languageEnglish
Pages (from-to)890-897
Number of pages8
JournalMolecular Pharmacology
Volume47
Issue number5
Publication statusPublished - May 1995

ASJC Scopus subject areas

  • Pharmacology

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