title: Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome.
abstract: OBJECTIVE
  The aim of this study was to investigate whether colonic mucosal N-methyl-D-aspartate receptor (NMDAR) participates in visceral hypersensitivity in irritable bowel syndrome (IBS).
  
  
  METHODS
  C57BL/6 mice were administered intrarectally with trinitrobenzenesulfonic acid (TNBS) for the establishment of an IBS-like visceral hypersensitivity model. Those received an equivalent volume of 50% ethanol were regarded as the controls. Abdominal withdrawal reflex (AWR) scores in response to colorectal distention (CRD) were used to assess visceral sensitivity. NMDAR levels in the colonic mucosa were detected by both immunohistochemistry and Western blot. The concentrations of glutamate and ammonia in the feces of the mice were measured. Changes in visceral sensitivity after the intracolonic administration of ammonia or NMDAR antagonist were recorded.
  
  
  RESULTS
  The established IBS-like mouse model of visceral hypersensitivity showed no evident inflammation in the colon. NMDAR levels in the colonic mucosa of the IBS-like mice were significantly higher compared with the controls, and were positively associated with AWR scores. The glutamate level in the feces of the TNBS-treated mice was similar to that of the controls, although the ammonia level was significantly higher. Intracolonic administration of ammonia induced visceral hypersensitivity in mice, which was repressed by pretreatment with NMDAR antagonist MK801.
  
  
  CONCLUSIONS
  Overexpressed NMDAR in the colonic mucosa may participate in the pathogenesis of visceral hypersensitivity in IBS. Our study identifies the effect of ammonia in the colonic lumen on NMDAR in the colonic mucosa as a potential novel targeted mechanism for IBS treatment.
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Qing Qing
authors.initials: QQ
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Fei Xue
authors.initials: FX
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Dong Yan
authors.initials: DY
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Li Xiang
authors.initials: LX
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yan Qing
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China. zuoxiuli@sina.com.
authors.forename: Xiu Li
authors.initials: XL
authors.lastname: Zuo
mesh_terms: D000641:Ammonia / Q000032:analysis; D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D004106:Dilatation / Q000379:methods; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D018698:Glutamic Acid / Q000032:analysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D017288:Pain Threshold / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D012018:Reflex / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid; D014781:Viscera / Q000503:physiopathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000641:Ammonia; D014302:Trinitrobenzenesulfonic Acid
keywords: N-methyl-D-aspartate receptor; colonic mucosa; irritable bowel syndrome; pathogenesis; visceral hypersensitivity