Nitric oxide mediates the sustained opening of NMDA receptor-gated ionic channels which follows transient excitotoxic exposure in hippocampal slices.
In the rat hippocampal slice, a brief exposure to glutamate and glycine increased MK-801 binding to 246% of controls. Increased binding persisted 90 min after removal of those amino acids from the incubation medium. Posttreatment with the competitive substrate inhibitor of nitric oxide synthase, N omega-nitro-L-arginine or with hemoglobin, which binds NO extracellularly, inhibited this postexcitotoxic increase in MK-801 binding. L-Arginine reversed this inhibitory effect but D-arginine did not. The combination of tetrodotoxin and low Ca2+, which blocks transmitter release prevented the poststimulation increase in MK-801 binding, suggesting a presynaptic component. These findings suggest that the sustained opening of NMDA receptor-gated ionic channels seen after transient glutamate/glycine stimulation is mediated by NO.
Brain Research Institute, UCLA School of Medicine 90024.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000633:toxicity*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018377:Neurotransmitter Agents / Q000633:toxicity; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D001120:Arginine