Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.
Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.
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瞬时受体电位锚蛋白 1 激动剂可改善术后肠梗阻小鼠模型中的肠道转运。
DOI：
10.1111/nmo.12877
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
T.
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文献类型：
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作者：
Tsuchiya;K.;Kubota;K.;Ohbuchi;K.;Kaneko;A.;Ohno;N.;Mase;A.;Matsushima;H.;Yamamoto;M.;Miyano;K.;Uezono;Y.;Kono;T.
研究背景瞬时受体电位锚蛋白1（transmittance receptor potential ankyrin 1，TRPA 1）在肠嗜铬细胞（enterochromiffin cell，ECC）中大量表达，其在体外收缩和在体胃肠道（vivogastrointestinal，GI）转运中的作用存在明显的矛盾。据报道，药用级日本传统药物大研中托（TU-100）有益于动物和人类的术后肠梗阻（POI），并加速GI转运。TU-100最近被证明通过刺激小肠上皮细胞（SI）中的TRPA 1来增加肠血流量。方法在操作诱导的小鼠POI模型、SI节段的体外培养和ECC模型细胞系RIN-14 B中检查各种TRPA 1激动剂对运动性的影响。TU-100成分，[6]-姜烯酚（6S）和γ-山椒醇（GS），改善了POI模型中的SI传输。在TRPA 1缺陷小鼠中，AITC、6S和GS的作用被消除，但CA未被消除。S1节段显示周期性蠕动运动活动，其周期性在TRPA 1缺陷型小鼠中消失。TU-100增强了运动性。AITC、CA和6S增加了分离的SI节段的5-HT释放，除CA外，所有这些化合物的作用在TRPA 1缺陷小鼠中均消失。6S和GS以剂量和TRPA 1依赖的方式诱导RIN-14 B细胞释放5-HT。结论与推论腔内TRPA 1刺激是胃肠道动力障碍的潜在治疗策略。需要进一步研究以确定5-HT和/或ECC是否参与TRPA 1对运动性的影响。
BackgroundStimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results inin vitrocontractility andin vivogastrointestinal (GI) transit evaluations. The pharmaceutical‐grade Japanese traditional medicine daikenchuto (TU‐100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU‐100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI).MethodsThe effects of various TRPA1 agonists on motility were examined in a manipulation‐induced murine POI model,in vitroculture of SI segments and an ECC model cell line, RIN‐14B.Key ResultsOrally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU‐100 ingredients, [6]‐shogaol (6S) andγ‐sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1‐deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1‐deficient mice. TU‐100 augmented the motility. AITC, CA and 6S increased 5‐HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1‐deficient mice. 6S and GS induced a release of 5‐HT from RIN‐14B cells in a dose‐ and TRPA1‐dependent manner.Conclusions & InferencesIntraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5‐HT and/or ECC are involved in the effect of TRPA1 on motility.