Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors.
To define the significance of glutamate ionotropic receptors in sPLA -mediated neuronal cell death we used the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist PNQX. In primary neuronal cell cultures both MK-801 and PNQX inhibited sPLA - and glutamate-induced neuronal death. [ H]Arachidonic acid release induced by both sPLA and glutamate was partially blocked by MK-801, indicating that the glutamate-NMDA-cPLA pathway contributes to sPLA -induced arachidonic acid release. Systemic administration of MK-801 to rats that had sPLA injected into the right striatum significantly decreased neuronal cell death. We conclude that glutamatergic synaptic activity modulates sPLA -induced neuronal cell death.
Kolko
Miriam
M
Lousiana State University Health Sciences Center, Neuroscience Center of Excellence and Department of Opthalmology, New Orleans, LA 70112, USA.
de Turco
Elena B
EB
Diemer
Nils Henrik
NH
Bazan
Nicolas G
NG
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000188:drug therapy / Q000201:enzymology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism; D005333:Fetus; D054501:Group II Phospholipases A2; D006801:Humans; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; C120005:PD 152247; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016718:Arachidonic Acid; D016291:Dizocilpine Maleate; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2