Omega-conotoxin GVIA protects against ischemia-induced neuronal death in the Mongolian gerbil but not against quinolinic acid-induced neurotoxicity in the rat.
Excessive release of neurotransmitters is reported to contribute to the delayed neuronal death in animal models of cerebral ischemia. Since evidence is accumulating that N-type voltage-sensitive calcium channels (N-channels) regulate the release of neurotransmitters, we investigated the effects of omega-conotoxin GVIA (omega-CTX), an antagonist of N-channels, on delayed neuronal death following transient ischemia in gerbils. Delayed neuronal death in the CA1 subfield of the hippocampus following 5-min ischemia was attenuated by omega-CTX in a dose-dependent manner when the agent was injected intracisternally 1 hr before ischemia was produced. However, omega-CTX failed to prevent neurotoxicity produced by a direct injection of quinolinic acid into the hippocampus in rats. These results suggest that omega-CTX has a neuroprotective effect against ischemic brain injury, which effect probably results from its inhibition of the excessive release of neurotransmitters, including excitatory amino acids, during ischemia.
Yamada
K
K
Department of Neuropsychopharmacology, Nagoya University School of Medicine, Japan.
Teraoka
T
T
Morita
S
S
Hasegawa
T
T
Nabeshima
T
T
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D020866:omega-Conotoxin GVIA; D017378:Quinolinic Acid