omega-agatoxin IVA and excitotoxicity in cortical neuronal cultures.
Because the P- and Q-type Ca2+ channel antagonist omega-agatoxin IVA inhibits glutamate release, agatoxin-related drugs could have a role in the treatment of excitotoxic neurologic disorders such as stroke. We examined the effect of omega-agatoxin IVA on excitotoxicity (lactate dehydrogenase release) induced by depolarization with veratridine or ouabain, or by N-methyl-D-aspartate, in neuron-enriched cerebral cortical cultures. omega-Agatoxin IVA (< or = 300 nM) failed to reduce excitotoxicity, as did the L-type Ca2+ channel antagonist nimodipine and the N-type antagonist omega-conotoxin GVIA. Drugs that inhibit glutamate release may not necessarily be neuroprotective.
Lustig
H S
HS
Department of Neurology, University of Pittsburgh School of Medicine, PA 15261, USA.
Ahern
K B
KB
Greenberg
D A
DA
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D018698:Glutamic Acid; D010042:Ouabain; D016202:N-Methylaspartate; D014701:Veratridine; D002118:Calcium