Abstract | BACKGROUND: 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. KEY 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 & INFERENCES: 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.
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Authors | G Varga, D Erces, B Fazekas, M Fülöp, T Kovács, J Kaszaki, F Fülöp, L Vécsei, M Boros |
Journal | Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
(Neurogastroenterol Motil)
Vol. 22
Issue 2
Pg. 217-25, e68
(Feb 2010)
ISSN: 1365-2982 [Electronic] England |
PMID | 19735360
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Excitatory Amino Acid Antagonists
- Receptors, N-Methyl-D-Aspartate
- SZR 72
- Tumor Necrosis Factor-alpha
- Trinitrobenzenesulfonic Acid
- Peroxidase
- Nitric Oxide Synthase
- Xanthine Oxidase
- Kynurenic Acid
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Topics |
- Analysis of Variance
- Animals
- Blood Pressure
(drug effects, physiology)
- Colitis
(chemically induced, metabolism, physiopathology)
- Colon
(drug effects, metabolism, physiopathology)
- Disease Models, Animal
- Excitatory Amino Acid Antagonists
(pharmacology)
- Gastrointestinal Motility
(drug effects, physiology)
- Inflammation
(metabolism, physiopathology)
- Kynurenic Acid
(analogs & derivatives, pharmacology)
- Male
- Nitric Oxide Synthase
(metabolism)
- Peroxidase
(metabolism)
- Random Allocation
- Rats
- Rats, Wistar
- Receptors, N-Methyl-D-Aspartate
(metabolism)
- Time Factors
- Trinitrobenzenesulfonic Acid
(toxicity)
- Tumor Necrosis Factor-alpha
(blood)
- Xanthine Oxidase
(metabolism)
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