Development of oral drug to induce defecation based on the effects that stimulation to intragastric cold receptors enhances colonic motility and induce defecations

基于刺激胃内冷感受器增强结肠蠕动并诱导排便的效果，开发口服诱导排便药物

• 批准号: 23591953
• 负责人: SHIBATA Chikashi
• 金额: $ 3.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591953/
• 关键词: 寒冷受容体; TRPA1; 結腸運動; 消化管運動

Intracolonic TRPA1 agonist allyl isothiocyanate (AITC) increased colonic motility and induced defecations in 75% of experiments in neurally intact dogs. These effects of AITC were inhibited by muscarinic, nicotinic, serotonergic, or TRPA1 antagonists but unaltered by TRPV1 antagonist. In dogs with transection/re-anasotomosis (T/R) between the proximal and middle colon, increase in colonic motility was inhibited in the middle-distal colon, while in dogs with extrinsic denervation, increase in colonic motility was inhibited in the distal colon. Frequency of defecations was decreased compared to neurally intact dogs in dogs with T/R and extrinsic denervation. These results indicate that intracolonic AITC stimulates colonic motility and defecation via cholinergic, serotonergic, and TRPA1 pathways. Continuity of colonic enteric neurons and extrinsic nerves play a role in intracolonic AITC-induced colonic motor response.

结肠内TRPA1激动剂异硫氰酸烯丙酯（AITC）在75%的实验中增加了神经完整犬的结肠运动和诱导排便。毒蕈碱、烟碱、血清素或TRPA1拮抗剂可抑制AITC的这些作用，但TRPV1拮抗剂未改变AITC的作用。在近端和中端结肠之间进行横断/再吻合（T/R）的犬中，结肠运动的增加在中端结肠受到抑制，而在外源性去神经支配的犬中，结肠运动的增加在远端结肠受到抑制。与神经完整的狗相比，T/R和外源性去神经的狗排便频率减少。这些结果表明，结肠内AITC通过胆碱能、血清素能和TRPA1途径刺激结肠运动和排便。结肠肠神经元和外源性神经的连续性在结肠内aitc诱导的结肠运动反应中起作用。