title: Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis.
abstract: OBJECTIVE
  To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and those with ulcerative colitis (UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan (5-HT) signaling pathway.
  
  
  METHODS
  Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor (3R), 4R, and 7R mRNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.
  
  
  RESULTS
  Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3R and 5-HT5R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7R expression.
  
  
  CONCLUSIONS
  The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7R expression in the colonic mucosa were significantly different between these groups. The results reveal that (1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and (2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Yu
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Shao-Gang
authors.initials: SG
authors.lastname: Huang
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Chi
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Ru-Xi
authors.initials: RX
authors.lastname: Lv
authors.affiliation: Feng-Yan Yu, Hong-Gang Chi, Ying Zou, Ru-Xi Lv, Xue-Bao Zheng, Traditional Chinese Medicine Institute, Guangdong Medical University, Dongguan 524023, Guangdong Province, China.
authors.forename: Xue-Bao
authors.initials: XB
authors.lastname: Zheng
mesh_terms: D006916:5-Hydroxytryptophan / Q000097:blood*; D015746:Abdominal Pain / Q000097:blood / Q000209:etiology; D000328:Adult; D003093:Colitis, Ulcerative / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D003672:Defecation; D003967:Diarrhea / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D007413:Intestinal Mucosa / Q000294:innervation / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058748:Pain Perception; D017288:Pain Threshold; D011446:Prospective Studies; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D055815:Young Adult
chemical_list: D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase
keywords: 5-Hydroxytryptophan; Diarrhea-predominant irritable bowel syndrome; Stomach type diarrhea; Ulcerative colitis in remission