Acute peroxide treatment of rat hippocampal slices induces adenosine-mediated inhibition of excitatory transmission in area CA1.
Brief exposure to conditions that generate free radicals inhibits synaptic transmission in hippocampal slices, most likely via a presynaptic mechanism. Because other physiologically stressful conditions that generate free radicals, such as hypoxia or ischemia, stimulate the release of adenosine from brain slices, we determined whether increases in extracellular adenosine mediate the presynaptic inhibition of excitatory transmission induced by peroxide treatment. Simultaneous addition of hydrogen peroxide (0.01%) and ferrous sulfate (100 microM) resulted in a >80% decrease in synaptic potentials recorded in the CA1 region of hippocampal slices of adult male rats. Treatment with theophylline (200 microM), a non-selective adenosine receptor antagonist, or 8-cyclopentyl-1,3-dipropylxanthine (100 nM), a selective adenosine A1 receptor antagonist, prior to and during hydrogen peroxide superfusion prevented the inhibition. These results demonstrate that acute exposure to hydrogen peroxide induces an adenosine-mediated decrease in synaptic transmission in hippocampal slices.
Masino
S A
SA
Department of Pharmacology and Neuroscience Program, UCHSC, Denver, CO 80262, USA. susan.masino@uchsc.edu
Mesches
M H
MH
Bickford
P C
PC
Dunwiddie
T V
TV
D000241:Adenosine / Q000378:metabolism*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005296:Ferrous Compounds / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D016877:Oxidants / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D005296:Ferrous Compounds; D016877:Oxidants; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; C020748:ferrous sulfate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D006861:Hydrogen Peroxide; D013806:Theophylline; D000241:Adenosine