Protective effect of the metabotropic glutamate receptor agonist, DCG-IV, against excitotoxic neuronal death.
(2S,1'R,2'R,3'R)-2-(2,3-Dicarboxycyclopropyl)glycine (DCG-IV), a potent agonist of subtypes 2 and 3 of metabotropic glutamate receptors (mGluR2 or 3), protected cultured cortical neurons against excitotoxicity induced either by a brief exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. As a neuroprotective agent, DCG-IV was much more potent than the mixed agonists 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) or (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), suggesting a neuroprotective role for mGluR2 or 3 against excitotoxic neuronal death.
Bruno
V
V
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Copani
A
A
Battaglia
G
G
Raffaele
R
R
Shinozaki
H
H
Nicoletti
F
F
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*
D000600:Amino Acids, Dicarboxylic; D003521:Cyclopropanes; D009498:Neurotoxins; D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C082313:2-(2,3-dicarboxycyclopropyl)glycine; C035261:(alpha-carboxycyclopropyl)glycine; D016202:N-Methylaspartate; D000242:Cyclic AMP; D007608:Kainic Acid; D015056:1-Methyl-3-isobutylxanthine; D005998:Glycine