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Group I metabotropic glutamate receptors participate in homocysteine‐evoked neurotoxicity
Author(s) -
Ziemińska E.,
Stafiej A.,
Łazarewicz J. W.
Publication year - 2003
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.1471-4159.85.s2.15_7.x
Subject(s) - neurotoxicity , metabotropic glutamate receptor , excitotoxicity , nmda receptor , glutamate receptor , metabotropic receptor , metabotropic glutamate receptor 2 , pharmacology , chemistry , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , receptor , homocysteine , medicine , biochemistry , toxicity
Homocysteine (HCY) neurotoxicity is known to be mediated by disturbances in methylation processes and by the NMDA receptor‐mediated excitotoxicity. In this study we examined the role of group I metabotropic glutamate receptors (mGlyRs) in HCY‐induced toxicity in cultured rat cerebellar granule neurons exhibited for 30 min, or cultured in the presence of HCY for 3 days. Acute neurodegeneration induced by >10 m m D,L‐HCY, or subchronic damage evoked by 75–500 µ m HCY were enhanced by 50 µ m glycine and moderately inhibited by 0.5 µ m MK‐801, revealing the NMDA receptor‐mediated portion of HCY neurotoxicity. Also group I mGluRs antagonists 25 µ m LY367385 or MPEP given alone only moderately inhibited acute and subchronic HCY neurotoxicity, but given together with MK‐801 completely prevented neurotoxicity. These results demonstrate that acute homocysteine‐induced neurotoxicity is mediated cooperatively by group I mGluRs and NMDA receptors.