Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs
Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs
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DOI：
10.1111/j.1365-2982.2007.00989.x
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发表时间：
2008-01-01
影响因子：
3.5
通讯作者：
Boros, M.
中科院分区：
文献类型：
--
作者：
Kaszaki, J.;Palasthy, Z.;Boros, M.
犬尿烯酸（KynA）是一种N-甲基-D-天冬氨酸（NMDA）谷氨酸受体的内源性拮抗剂，在兴奋性毒性神经系统疾病中保护中枢神经系统。我们假设KynA对肠道谷氨酸受体的抑制可能会影响胃肠道的动力障碍。第1组为假手术对照组，第2组为KynA治疗组，第3、4组为机械性结肠梗阻7 h。第4组在肠梗阻发作时接受KynA治疗。监测血流动力学和运动变化，并从组织样品中测定黄嘌呤氧化还原酶（XOR）和髓过氧化物酶（MPO）的活性。结肠梗阻引起高动力循环反应，运动指数显著升高，粘膜白细胞积聚和XOR活性增加。KynA治疗增强了结肠的张力，永久性地降低了巨大结肠收缩的运动指数，并减少了XOR和MPO活性的增加。这些作用与体外抑制XOR活性是同时发生的。总之，KynA拮抗结肠阻塞诱导的运动反应和XOR激活。抑制肠道NMDA受体可能提供一种选择，影响肠道运动过度和炎症变化。
Kynurenic acid (KynA), an endogenous antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors, protects the central nervous system in excitotoxic neurological diseases. We hypothesized that the inhibition of enteric glutamate receptors by KynA may influence dysmotility in the gastrointestinal tract. Group 1 of healthy dogs served as the sham-operated control, in group 2, the animals were treated with KynA, while in groups 3 and 4 mechanical colon obstruction was maintained for 7 h. Group 4 was treated with KynA at the onset of ileus. Hemodynamics and motility changes were monitored, and the activities of xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) were determined from tissue samples. Colon obstruction induced a hyperdynamic circulatory reaction, significantly elevated the motility index and increased the mucosal leucocyte accumulation and the XOR activity. The KynA treatment augmented the tone of the colon, permanently decreased the motility index of the giant colonic contractions and reduced the increases in XOR and MPO activities. These effects were concomitant with the in vitroinhibition of XOR activity. In conclusion, KynA antagonizes the obstruction-induced motility responses and XOR activation in the colon. Inhibition of enteric NMDA receptors may provide an option to influence intestinal hypermotility and inflammatory changes.