标题：Vasopressin augments TNBS-induced colitis through enteric neuronal V-1a receptor-mediated COX-2-dependent prostaglandin release from mast cells in mice
作者：Dou, Dandan; Chen, Lixin; Di, Hong; Song, Zhuoran; Li, Shirui; Bu, Xinjie; Dai, Qing; Wang, Shuai; Li, Jing Xin; Zhu, Xiaolong; Ji 更多 作者机构：[Dou, Dandan; Li, Jing Xin] Shandong Univ, Sch Basic Med Sci, Dept Physiol, Jinan, Shandong, Peoples R China.; [Chen, Lixin; Di, Hong; Song, Zhuoran 更多
通讯作者：Zhu, XL;Jing, HY
通讯作者地址：[Zhu, XL]Shandong Univ, Shandong Prov Hosp, Dept Cardiac Surg, Jinan, Shandong, Peoples R China;[Jing, HY]Shandong Univ, Shandong Prov Hosp, Dept Path 更多
来源：NEUROGASTROENTEROLOGY AND MOTILITY
关键词：cholinergic neuron; inflammatory bowel disease; mast cell; permeability;; prostaglandin; vasopressin
摘要：Background Inflammatory bowel disease (IBD) is a functional disorder with chronic and relapsing clinical features. Vasopressin (VP) is a hormone responsible for water and stress homeostasis and also regulates gastrointestinal inflammation and motility. We explored whether VP was related to IBD pathogenesis and its possible pathway. Methods Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice. The disease activity and colonic damage were evaluated through a scoring system. Locations of the V-1a receptor were revealed by immunochemistry method in colon. Ussing chamber technique was performed for the electrophysiological characterization by using rat ileum. The (Arg(8))-Vasopressin (AVP)-evoked short-circuit current (Isc) was recorded in the presence of conivaptan (V-1a and V-2 receptor antagonist), tolvaptan (V-1b receptor antagonist), tetrodotoxin (TTX), atropine, cyclooxygenase (COX) inhibitors (indomethacin, nonspecific COX antagonist; SC560, COX-1 antagonist; NS560, COX-2 antagonist), and a stabilizer of mast cell (cromolyn sodium), respectively. Key Results TNBS resulted in the obvious loss of body weight and tissue damages in mice. AVP significantly aggravated the TNBS-induced colitis, which was attenuated by conivaptan but not tolvaptan. V-1a receptors were found immunopositive in neurons among the enteric nervous system. AVP evoked a pulsatile response in Isc. Its amplitude, frequency, and cycle duration were around 8-15 mu A/cm(2), 10-11 mHz, and 1.5 minutes, respectively. Notably, the AVP-evoked change in Isc was abolished by TTX, atropine, conivaptan, indomethacin, NS560, and cromolyn sodium, respectively. Conclusions and Inferences VP-V-1a receptor played the proinflammatory role in TNBS-induced colitis by promoting COX-2-dependent prostaglandin release from mucosal mast cells, which was mediated by the cholinergic pathway.