title: Colonic N-methyl-d-aspartate receptor contributes to visceral hypersensitivity in irritable bowel syndrome.
abstract: OBJECTIVE
  N-methyl-d-aspartate receptor (NMDAR) in brain, spinal cord, and enteric nervous system is involved in visceral hypersensitivity. This study aimed to reveal the functional expression of NMDAR on mucosal cells in colon and to investigate the downstream signal pathway from colonic NMDAR activation to visceral hypersensitivity in irritable bowel syndrome (IBS).
  
  
  METHODS
  The expression of mucosal NMDAR in IBS patients and healthy controls was assessed by immunohistochemistry and Western blot and correlated with abdominal pain/discomfort scores quantified by a validated questionnaire. Electromyography recording in response to colorectal distension was recorded to measure the colonic sensitivity of mice receiving NMDA administration intracolonically. Brain-derived neurotrophic factor (BDNF) expression and extracellular signal-regulated kinase (ERK) pathway activation were examined in human colonic epithelial HT29 cells after NMDA stimulation, with or without MK801 or U0126 pretreatment.
  
  
  RESULTS
  A significant upregulation of mucosal NMDAR was observed in IBS patients compared with controls, which was significantly correlated with abdominal pain/discomfort scores. Intracolonic administration of NMDA in normal mice produced increased colonic sensitivity to colorectal distension and elevated expression of BDNF and activation of ERK. Activation of NMDAR in colonic epithelial HT29 cells in vitro induced increased BDNF secretion in cell supernatants and higher BDNF expression in cells, as well as elevated phosphorylated ERK.
  
  
  CONCLUSIONS
  This study demonstrated that the activation of mucosal NMDAR in colon may contribute to the visceral hypersensitivity in IBS, by increasing production of BDNF in an ERK-dependent pathway.
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Qingqing
authors: Q
authors: Qi
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Feixue
authors: F
authors: Chen
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Wenxue
authors: W
authors: Zhang
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Peng
authors: P
authors: Wang
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Yanqing
authors: Y
authors: Li
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Xiuli
authors: X
authors: Zuo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D011795:Surveys and Questionnaires; D015854:Up-Regulation; D014781:Viscera / Q000503:physiopathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate
keywords: N-methyl-d-aspartate receptor; brain-derived neurotrophic factor; colon mucosa; irritable bowel syndrome; visceral hypersensitivity