Activation of hippocampal metabotropic excitatory amino acid receptors leads to seizures and neuronal damage.
A role for ionotropic (NMDA, AMPA, and kainate) excitatory amino acid (EAA) receptors in seizure and seizure-related brain damage is well documented. To study the possible role of metabotropic (G-protein linked) EAA receptors in this regard, a highly selective metabotropic EAA agonist was injected into the hippocampus of halothane-anesthetized rats. This resulted in delayed-onset seizures and selective hippocampal neuronal damage that was indirectly mediated by NMDA receptors. This provides direct evidence for a novel role of metabotropic EAA receptors in the etiology of seizures and neuronal damage.
Sacaan
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AI
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Schoepp
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DD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001711:Biotransformation; D016923:Cell Death / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D017459:Receptors, Amino Acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D019204:GTP-Binding Proteins