There is a growing awareness of the role that TRP channels play in regulating sensory and motor functions in the gastrointestinal tract. In this study we used an in-vitro murine model of colonic peristaltic-like complexes (CPMCs) to evaluate the role of exogenous and endogenous TRPA1 signaling processes in regulating colonic motility. Using in-vitro recordings of intraluminal pressure to monitor the presence of CPMCs in colonic segments we performed a series of experiments on male CD1 mice (2 months of age) and found that CPMC activity was attenuated by TRPA1 agonists. Bath application of the TRPA1 antagonist HC-030031 had no effect upon basal CPMC activity whereas application of the synthetic TRPA1 agonist ASP7663 caused a reversible dose dependent decrease in CPMC frequency that was blocked by HC-030031. Cinnamaldehyde and 4-hydroxy-2-nonenal elicited long lasting decreases in CPMC frequency that were blocked by HC-030031 whereas the decreased CPMC activity invoked by AITC could not be blocked by HC-030031. Our results show that any potential mechanosensory function of TRPA1 doesn’t involve contributing to distension induced colonic motor activity and that a role for TRPA1 in the colon is through regulating motility through exogenous and endogenous agonist induced inhibitory effects.

中文翻译：

---

TRPA1 通道激活抑制小鼠结肠的运动活动

人们越来越意识到 TRP 通道在调节胃肠道的感觉和运动功能中所起的作用。在这项研究中，我们使用结肠蠕动样复合物 (CPMC) 的体外小鼠模型来评估外源性和内源性 TRPA1 信号传导过程在调节结肠运动中的作用。我们使用腔内压力的体外记录来监测结肠段中 CPMC 的存在，我们对雄性 CD1 小鼠（2 个月大）进行了一系列实验，发现 CPMC 活性被 TRPA1 激动剂减弱。TRPA1 拮抗剂 HC-030031 的浴应用对基础 CPMC 活性没有影响，而合成 TRPA1 激动剂 ASP7663 的应用导致 CPMC 频率的可逆剂量依赖性降低，这被 HC-030031 阻断。肉桂醛和 4-羟基-2-壬烯醛引起 CPMC 频率的长期持续降低，被 HC-030031 阻断，而 AITC 引起的 CPMC 活性降低不能被 HC-030031 阻断。我们的结果表明，TRPA1 的任何潜在机械感觉功能不涉及促进膨胀诱导的结肠运动活动，并且 TRPA1 在结肠中的作用是通过外源性和内源性激动剂诱导的抑制作用调节运动。