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Activation of Metabotropic Glutamate Receptors Prevents Neuronal Apoptosis in Culture
Author(s) -
Copani Agata,
Bruno Valeria M. G.,
Barresi Vincenza,
Battaglia Giuseppe,
Condorelli Daniele F.,
Nicoletti Ferdinando
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64010101.x
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 1 , metabotropic receptor , metabotropic glutamate receptor 6 , glutamate receptor , acpd , metabotropic glutamate receptor 5 , agonist , biology , metabotropic glutamate receptor 2 , metabotropic glutamate receptor 7 , receptor , microbiology and biotechnology , biochemistry , chemistry
Cultured granule cells grown in serum‐containing medium with a “low K + ” concentration (10 m M ) underwent apoptosis after maturation for 5 days in vitro (5 DIV), a time that coincides with the developmental decline in the activity of metabotropic glutamate receptors (mGluRs) coupled to polyphosphoinositide hydrolysis. The mGluR agonist (1 S ,3 R )‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1 S ,3 R ‐ACPD) prevented the development of low K + ‐induced apoptosis and the presence of the drug was critical at 6 and 7 DIV, i.e., after the drop of mGluR activity. The neuroprotective action of 1 S ,3 R ‐ACPD was prevented by the mGluR antagonist ( RS )‐α‐methyl‐4‐carboxyphenylglycine (MCPG) and was mimicked by N ‐methyl‐ d ‐aspartate or carbamylcholine but not by agonists of the mGluR subtypes negatively linked to adenylyl cyclase. In cultures treated either with Li + —which reduced polyphosphoinositide response to concentrations of glutamate (5 µ M ) that approximate those physiologically present in the incubation medium—or MCPG, the development of low K + ‐induced apoptosis already occurred at 4 DIV. Thus, the activation of mGluRs coupled to polyphosphoinositide hydrolysis by endogenous glutamate could contribute to protect cultured granule cells against apoptosis during early stages of maturation.