@article {Copani890, author = {A Copani and V Bruno and G Battaglia and G Leanza and R Pellitteri and A Russo and S Stanzani and F Nicoletti}, title = {Activation of metabotropic glutamate receptors protects cultured neurons against apoptosis induced by beta-amyloid peptide.}, volume = {47}, number = {5}, pages = {890--897}, year = {1995}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Prolonged exposure of cultured cortical cells or cultured cerebellar granule cells to the residue 25-35 fragment of beta-amyloid peptide (beta AP), beta AP(25-35), induced neuronal apoptosis, as revealed by morphological analysis, fluorescent chromatin staining, and immunodetection of oligonucleosomes released from the nucleus into the cytoplasm. beta AP(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)-alpha-methyl-4-carboxyphenylglycine and was mimicked by (2S,1{\textquoteright}R,2{\textquoteright}R,3{\textquoteright}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{\textquoteright}R,2{\textquoteright}R,3{\textquoteright}R)-2-(2,3-dicarboxycyclopropyl)glycine] reduced beta AP(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 beta AP(25-35)-induced apoptosis.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/47/5/890}, eprint = {https://molpharm.aspetjournals.org/content/47/5/890.full.pdf}, journal = {Molecular Pharmacology} }