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

J. Kaszaki, Dániel Érces, Gabriella Varga, Andrea Szabó, L. Vécsei, M. Borós

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)211-223
Number of pages13
JournalJournal of Neural Transmission
Volume119
Issue number2
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Kynurenine
Synaptic Transmission
Kynurenic Acid
Gastrointestinal Motility
Gastrointestinal Diseases
Inflammation
Nervous System
Small Intestine
Glutamic Acid
Xanthine Dehydrogenase
Nitric Oxide Synthase Type I
Investigational Therapies
Acute Disease
Tryptophan
Superoxides
Chronic Disease
Cell Death
Animal Models
Therapeutics
Neuroprotection

Keywords

  • Inflammation
  • Intestinal motility
  • Kynurenic acid
  • N-methyl-d-aspartate receptors

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Kynurenines and intestinal neurotransmission : The role of N-methyl-d-aspartate receptors. / Kaszaki, J.; Érces, Dániel; Varga, Gabriella; Szabó, Andrea; Vécsei, L.; Borós, M.

In: Journal of Neural Transmission, Vol. 119, No. 2, 02.2012, p. 211-223.

Research output: Contribution to journalArticle

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