Biphasic effect of hydrogen peroxide on field potentials in rat hippocampal slices.
In the CA1 region of rat hippocampal slices, H2O2 (0.294-2.94 mM) caused initial augmentation, and subsequent long-lasting depression, of population spikes and excitatory postsynaptic potentials. The effect of H2O2 may not be mediated by its degradation product, hydroxyl radicals, because an iron chelator deferoxamine did not block the effect. A catalase inhibitor 3-amino-1,2,4-triazole only modestly attenuated the initial augmentation, suggesting that the effect of H2O2 is not attributable to catalase-dependent O2 generation, either. An N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid had no influence on the effect of H2O2, whereas a gamma-aminobutyric acid type A receptor channel blocker picrotoxin attenuated long-lasting depression, indicating that gamma-aminobutyric acid-mediated inhibition is altered during the depression phase. The initial augmentation but not subsequent depression was attenuated by a phospholipase A2/C inhibitor 4-bromophenacyl bromide, suggesting the involvement of lipid signaling molecule(s) in the enhancement of excitatory synaptic transmission. These results suggest that H2O2 regulates hippocampal synaptic transmission via multiple mechanisms.
Katsuki
H
H
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Nakanishi
C
C
Saito
H
H
Matsuki
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases