Activation of group III metabotropic glutamate receptors is neuroprotective in cortical cultures.
(RS)-alpha-Methyl-4-phosphonophenylglycine (MPPG) and (S)-alpha-methyl-3-carboxyphenylalanine (M3CPA), two novel preferential antagonists of group III metabotropic glutamate (mGlu) receptors, antagonized the neuroprotective activity of L-2-amino-4-phosphono-butanoate (L-AP4) or L-serine-O-phosphate in mice cultured cortical cells exposed to a toxic pulse of N-methyl-D-aspartate. In contrast, MPPG did not influence the neuroprotective activity of the selective group II mGlu receptor agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxy-cyclopropyl) glycine (DCG-IV). These results indicate that activation of group III mGu receptors exerts neuroprotective activity against excitotoxic neuronal death. At least one of the two major group III mGlu receptor subtypes, i.e. mGlu4 receptor, is expressed by cultured cortical neurons, as shown by immunocytochemical analysis with specific polyclonal antibodies.
Bruno
V
V
Instituto Mediterraneo di Neuroscienze Neuromed, Pozzilli, Italy.
Copani
A
A
Bonanno
L
L
Knoepfel
T
T
Kuhn
R
R
Roberts
P J
PJ
Nicoletti
F
F
D000409:Alanine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology; D011817:Rabbits; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology
D018094:Receptors, Metabotropic Glutamate; C101185:alpha-methyl-4-phosphonophenylglycine; C103199:alpha-methyl-3-carboxyphenylalanine; D010649:Phenylalanine; D016202:N-Methylaspartate; D000409:Alanine