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Journal of Neural Transmission

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01.02.2012 | Basic Neurosciences, Genetics and Immunology - Review article

Kynurenines and intestinal neurotransmission: the role of N-methyl-d-aspartate receptors

verfasst von: József Kaszaki, Dániel Érces, Gabriella Varga, Andrea Szabó, László Vécsei, Mihály Boros

Erschienen in: Journal of Neural Transmission | Ausgabe 2/2012

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Abstract

Gastrointestinal neuroprotection involves the net effect of many mechanisms which protect the enteral nervous system and its cells from death, dysfunction or degeneration. Neuroprotection is also a therapeutic strategy, aimed at slowing or halting the progression of primary neuronal loss following acute or chronic diseases. The neuroprotective properties of a compound clearly have implications for an understanding of the mechanism of dysfunctions and for therapeutic approaches in a number of gastrointestinal diseases.

This paper focused on the roles of glutamate and N-methyl-d-aspartate (NMDA) receptors in the intrinsic neuronal control of gastrointestinal motility; the consequences of inflammation on gastrointestinal motility changes; and the involvement of tryptophan metabolites (especially kynurenic acid) in the regulatory function of the enteral nervous system and the modulation of the inflammatory response. Common features in the mechanisms of action, illustrative evidence from animal models, and experimental neuroprotective therapies making use of the currently available possibilities are also discussed.

Overall, the evidence suggests that gastrointestinal neuroprotection against inflammation and glutamate-induced neurotoxicity may be mediated synergistically through the blockade of NMDA receptors and the inhibition of neuronal nitric oxide synthase activity and xanthine oxidoreductase-dependent superoxide production. These components are likewise significant factors in the pathomechanism of gastrointestinal inflammatory diseases and inflammation-linked motility alterations. Inhibition of the enteric NMDA receptors by kynurenic acid or its analogues may provide a novel option via which to influence intestinal hypermotility and inflammatory processes simultaneously.

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Titel: Kynurenines and intestinal neurotransmission: the role of N-methyl-d-aspartate receptors
verfasst von: József Kaszaki
Dániel Érces
Gabriella Varga
Andrea Szabó
László Vécsei
Mihály Boros
Publikationsdatum: 01.02.2012
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 2/2012
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-011-0658-x

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