Institute of Surgical Research, Szent-Györgyi Albert Medical and Pharmaceutical Centre, University of Szeged, Szeged, Hungary.
Neurogastroenterol Motil. 2010 Feb;22(2):217-25, e68. doi: 10.1111/j.1365-2982.2009.01390.x. Epub 2009 Sep 3.
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.
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.
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.
炎症性肠病伴有严重的运动障碍。我们的研究目的是探讨外周 N-甲基-D-天冬氨酸（NMDA）敏感型谷氨酸受体（NMDA-R）阻断是否会改变化学诱导的急性结肠炎中的运动变化，以及这种调节是如何实现的。
在麻醉的 Wistar 大鼠中，用天然 NMDA-R 拮抗剂 kynurenic 酸（KynA）或血脑屏障可渗透的合成 KynA 类似物 SZR-72 处理后，研究 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎中的炎症和运动变化。宏观血液动力学、浆膜微循环（通过活体视频显微镜观察）、肿瘤坏死因子-α（TNF-α）的血浆水平、炎症酶活性（黄嘌呤氧化还原酶（XOR）、髓过氧化物酶（MPO）和一氧化氮合酶（NOS））以及结肠运动（用应变计技术）在结肠炎诱导后 17 小时进行评估，并与对照条件进行比较。
TNBS 灌肠引起全身高动力循环反应，增加浆膜毛细血管血流，显著提高粘膜 XOR、MPO 和 NOS 活性，并增加与对照相比的结肠运动。用 KynA 或 SZR-72 进行 NMDA-R 拮抗剂治疗可显著降低 XOR、NOS 和 MPO 活性，降低运动并增加结肠张力。
这些数据表明 NMDA-R 在 TNBS 结肠炎中改变结肠运动中存在潜在的调节机制。抑制肠内 NMDA-R 可能通过同时影响肠道蠕动、微循环变化和炎症激活提供一种治疗选择。
