Exacerbation of neuronal cell death by activation of group 1 metabotropic glutamate receptors: Role of NMDA receptors and arachidonic acid release

Citation
Jw. Allen et al., Exacerbation of neuronal cell death by activation of group 1 metabotropic glutamate receptors: Role of NMDA receptors and arachidonic acid release, EXP NEUROL, 169(2), 2001, pp. 449-460
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EXPERIMENTAL NEUROLOGY
ISSN journal
0014-4886 → ACNP
Volume
169
Issue
2
Year of publication
2001
Pages
449 - 460
Database
ISI
SICI code
0014-4886(200106)169:2<449:EONCDB>2.0.ZU;2-6
Abstract
Both ionotropic and metabotropic glutamate receptors have been implicated i n the pathogenesis of neuronal injury, Activation of group I metabotropic g lutamate receptors (mGluR) exacerbates neuronal cell death, whereas inhibit ion is neuroprotective. However, the mechanisms involved remain unknown. Ac tivation of group I mGluR modulates multiple signal transduction pathways i ncluding stimulation of phosphoinositide hydrolysis, potentiation of NMDA r eceptor activity, and release of arachidonic acid. Here we demonstrate that whereas activation of group I mGluR by (S)-3,5-dihydroxyphenylglycine (DHP G) potentiates NMDA-induced currents and intracellular calcium increases in rat cortical neuronal cultures, partial effects of group I mGluR activatio n or inhibition on neuronal injury induced by oxygen-glucose deprivation re main despite NMDA receptor blockade. DHPG stimulation also increases basal arachidonic acid release from rat neuronal-glial cultures and potentiates i njury-induced arachidonic acid release in these cultures. Thus, activation of group I mGluR may exacerbate neuronal injury through multiple mechanisms , which include positive modulation of NMDA receptors and enhanced release of arachidonic acid. (C) 2001 Academic Press.