mGluR modulation of post-traumatic neuronal death: role of NMDA receptors.
The potential interaction between group I metabotropic glutamate receptors (mGluR) and NMDA receptors in mediating of post-traumatic neuronal death was studied using an in vitro trauma model. Treatment with group I mGluR antagonists provided significant neuroprotection either in the presence or absence of an NMDA receptor antagonist. In contrast, treatment with a group I mGluR agonist alone significantly exacerbated injury; this exacerbation was significantly, but incompletely, reduced in the presence of an NMDA receptor antagonist. These findings are consistent with the conclusion that the effects of group I mGluR activation on post-traumatic cell death are mediated only in part through NMDA receptor modulation and suggest that group I mGluR antagonists may have important therapeutic potential.
Mukhin
A G
AG
Georgetown University Medical Center, Institute for Cognitive and Computational Sciences, Washington, DC 20007, USA.
Ivanova
S A
SA
Faden
A I
AI
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology / Q000502:physiology; D018920:Coculture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase; D008959:Models, Neurological; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology
C095756:1-aminoindan-1,5-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D005998:Glycine