title: N-Methyl-D-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat.
abstract: BACKGROUND
  Inflammatory bowel diseases are accompanied by severe motility disorders. The aim of our study was to investigate whether the blockade of peripheral N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors (NMDA-Rs) alters motility changes in chemically induced acute colitis and how this modulation is accomplished.
  
  
  METHODS
  The inflammatory and motility changes in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis were studied in anaesthetized Wistar rats following treatment with the natural NMDA-R antagonist kynurenic acid (KynA) or SZR-72, a blood-brain barrier-permeable synthetic KynA analogue. The macrohaemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), plasma levels of tumour necrosis factor alpha (TNF-alpha), inflammatory enzyme activities (xanthine oxidoreductase (XOR), myeloperoxidase (MPO) and nitric oxide synthase (NOS)), and colonic motility (with a strain-gauge technique) were evaluated 17 h after colitis induction and compared with the control conditions.
  
  
  RESULTS
  The TNBS enema induced a systemic hyperdynamic circulatory reaction, increased the serosal capillary blood flow, significantly elevated the mucosal XOR, MPO and NOS activities and augmented the colonic motility relative to the controls. The NMDA-R antagonist treatment with KynA or SZR-72 significantly reduced the XOR, NOS and MPO activities, decreased the motility and increased the tone of the colon.
  
  
  CONCLUSIONS
  These data demonstrate a potential modulatory mechanism of NMDA-R in altered colonic motility in TNBS colitis. Inhibition of the enteric NMDA-Rs may provide a therapeutic option via which to influence intestinal hypermotility, microcirculatory changes and inflammatory activation simultaneously.
authors.affiliation: Institute of Surgical Research, Szent-Györgyi Albert Medical and Pharmaceutical Centre, University of Szeged, Szeged, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Varga
authors.forename: D
authors.initials: D
authors.lastname: Erces
authors.forename: B
authors.initials: B
authors.lastname: Fazekas
authors.forename: M
authors.initials: M
authors.lastname: Fülöp
authors.forename: T
authors.initials: T
authors.lastname: Kovács
authors.forename: J
authors.initials: J
authors.lastname: Kaszaki
authors.forename: F
authors.initials: F
authors.lastname: Fülöp
authors.forename: L
authors.initials: L
authors.lastname: Vécsei
authors.forename: M
authors.initials: M
authors.lastname: Boros
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C533052:SZR 72; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D007736:Kynurenic Acid