| Enzymatic Transamination of D-Kynurenine Generates Kynurenic Acid in Rat and Human Brain. | |
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MedLine Citation:
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PMID: 22224417 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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In the mammalian brain, the α7 nicotinic and NMDA receptor antagonist kynurenic acid is synthesized by irreversible enzymatic transamination of the tryptophan metabolite L-kynurenine. D-kynurenine, too, serves as a bioprecursor of kynurenic acid in several organs including the brain, but the conversion is reportedly catalyzed through oxidative deamination by D-aminoacid oxidase. Using brain and liver tissue homogenates from rats and humans, and conventional incubation conditions for kynurenine aminotransferases, we show here that KYNA production from D-kynurenine, like the more efficient kynurenic acid synthesis from L-kynurenine, is blocked by the aminotransferase inhibitor aminooxyacetic acid. In vivo, focal application of 100 μM D-kynurenine by reverse microdialysis led to a steady rise in extracellular kynurenic acid in the rat striatum, causing a 4-fold elevation after 2 h. Attesting to functional significance, this increase was accompanied by a 36% reduction in extracellular dopamine. Both of these effects were duplicated by perfusion of 2 μM L-kynurenine. Co-infusion of aminooxyacetic acid (2 mM) significantly attenuated the in vivo effects of D-kynurenine and essentially eliminated the effects of L-kynurenine. Thus, enzymatic transamination accounts in part for kynurenic acid synthesis from D-kynurenine in the brain. These results are discussed with regard to implications for brain physiology and pathology. © 2012 The Authors Journal of Neurochemistry© 2012 International Society for Neurochemistry. |
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Authors:
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Veronica Pérez-de la Cruz; Laura Amori; Korrapati V Sathyasaikumar; Xiaodan Wang; Francesca M Notarangelo; Hui-Qiu Wu; Robert Schwarcz |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-7 |
Journal Detail:
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Title: Journal of neurochemistry Volume: - ISSN: 1471-4159 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry. |
Affiliation:
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Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland (USA). |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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