A metabotropic glutamate receptor agonist does not mediate neuronal degeneration in cortical culture.
In light of the evidence that calcium plays a critical role in excitotoxic neuronal death, it has been speculated that the metabotropic glutamate receptor may also contribute to excitotoxic damage through the mobilization of Ca2+ from intracellular stores. In the present study we examined this possibility by studying the neurotoxicity of trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD), a selective agonist of the metabotropic glutamate receptor. Exposure of cortical neurons to 100 microM trans-ACPD substantially increased phosphoinositide hydrolysis and intraneuronal free calcium in the presence of CPP and CNQX. Despite the presence of functional metabotropic receptors on cultured neurons, however, exposure of cultures to as high as 1 mM trans-ACPD for 24 h failed to produce any morphological or chemical signs of neuronal damage. Furthermore, trans-ACPD did not potentiate submaximal neurotoxicity produced by other non-N-methyl-D-aspartate (NMDA) agonists, kainate and D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA).
Koh
J Y
JY
Department of Psychobiology, University of California Irvine 92717.
Palmer
E
E
Lin
A
A
Cotman
C W
CW
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004622:Embryo, Mammalian; D005971:Glutamates / Q000502:physiology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D009498:Neurotoxins; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007770:L-Lactate Dehydrogenase; D007608:Kainic Acid