Involvement of the NMDA receptor/nitric oxide signal pathway in platelet-activating factor-induced neurotoxicity.
Platelet-activating factor (PAF), a bioactive phospholipid implicated in neuronal excitotoxic death, augments the presynaptic release of glutamate. Excessive activation of postsynaptic glutamate receptors and subsequent downstream signals leads to excitotoxicity. The present study proposed that the NMDA receptor/nitric oxide (NO) signal pathway might be involved in PAF-induced neurotoxicity. After the cultured neurons were exposed to PAF for 24 h the percentage of neuronal death increased in a dose-dependent manner. The PAF effects were significantly prevented not only by BN52021, a PAF antagonist, but also by MK-801, an NMDA antagonist, and L-NAME, an NO synthase (NOS) inhibitor. Moreover, the increases in NOS activity and neuronal NOS expression induced by chronic exposure of the cultured neurons to PAF were dramatically blocked by BN52021 and MK-801, respectively. Our findings suggest that the NMDA receptor/NO signaling pathway might contribute to the pathological mechanism of cell death triggered via PAF receptor activation.
Xu
Yun
Y
Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University School of Medicine, Nanjing University, Nanjing 210000, PR China.
Tao
Yuan-Xiang
YX
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004224:Diterpenes; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D046934:Ginkgolides; D007783:Lactones; D009498:Neurotoxins; D010972:Platelet Activating Factor; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; C045856:ginkgolide B; D019001:Nitric Oxide Synthase