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Reactive Oxygen Species Induced by Presynaptic Glutamate Receptor Activation is Involved in [(3)H]GABA Release from Rat Brain Cortical Nerve Terminals.
MedLine Citation:
PMID:  22864357     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We investigated the production of reactive oxygen species (ROS) as a response to presynaptic glutamate receptor activation, and the role of ROS in neurotransmitter (GABA) release. Experiments were performed with rat brain cortical synaptosomes using glutamate, NMDA and kainate as agonists of glutamate receptors. ROS production was evaluated with the fluorogenic compound dichlorodihydrofluorescein diacetate (H(2)DCF-DA), and GABA release was studied using synaptosomes loaded with [(3)H]GABA. All agonists were found to stimulate ROS production, and specific antagonists of NMDA and kainate/AMPA receptors, dizocilpine hydrogen maleate (MK-801) and 6-cyano-7-nitroquinoxaline-2,3-done (CNQX), significantly inhibited the ROS increase. Spontaneous as well as agonist-evoked ROS production was effectively attenuated by diphenylene iodonium (DPI), a commonly used potent inhibitor of NADPH oxidase activity, that suggests a high contribution of NADPH-oxidase to this process. The replacement of glucose with pyruvate or the simultaneous presence of both substrates in the medium led to the decrease in spontaneous and NMDA-evoked ROS production, but the increase in ROS production induced by kainate. Scavenging of agonist-evoked ROS production by a potent antioxidant N-acetylcysteine was tightly correlated with the inhibition of agonist-evoked GABA release. Together, these findings show that the activation of presynaptic glutamate receptors induces an increase in ROS production, and there is a tight correlation between ROS production and GABA secretion. The pivotal role of kainate/AMPA receptors in ROS production is under discussion.
Authors:
A Tarasenko; O Krupko; N Himmelreich
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-1
Journal Detail:
Title:  Neurochemistry international     Volume:  -     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Leontovich Str. 9, Kyiv 01601, Ukraine.
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