title: Alterations in serotonin, transient receptor potential channels and protease-activated receptors in rats with irritable bowel syndrome attenuated by Shugan decoction.
abstract: OBJECTIVE
  To determine the molecular mechanisms of Shugan decoction (SGD) in the regulation of colonic motility and visceral hyperalgesia (VHL) in irritable bowel syndrome (IBS).
  
  
  METHODS
  The chemical compounds contained in SGD were measured by high-performance liquid chromatography. A rat model of IBS was induced by chronic water avoidance stress (WAS). The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension. Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-α in colonic tissue and calcitonin-gene-related peptide (CGRP) in serum were measured by ELISA. The protein expression of serotonin [5-hydroxytryptamide (5-HT)], serotonin transporter (SERT), chromogranin A (CgA) and CGRP in colon tissue was measured by immunohistochemistry.
  
  
  RESULTS
  SGD inhibited colonic motility dysfunction and VHL in rats with IBS. Blockers of transient receptor potential (TRP) vanilloid 1 (TRPV1) (Ruthenium Red) and TRP ankyrin-1 (TRPA1) (HC-030031) and activator of protease-activated receptor (PAR)4 increased the pain pressure threshold, whereas activators of PAR2 and TRPV4 decreased the pain pressure threshold in rats with IBS. The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1 (capsaicin), TRPV4 (RN1747), TRPA1 (Polygodial) and PAR2 (AC55541). In addition, CGRP levels in serum and colonic tissue were both increased in these rats. TNF-α level in colonic tissue was also significantly upregulated. However, the levels of 5-HT, SERT and CgA in colonic tissue were decreased. All these pathological changes in rats with IBS were attenuated by SGD.
  
  
  CONCLUSIONS
  SGD alleviated VHL and attenuated colon motility in IBS, partly by regulating TRPV1, TRPV4, TRPA1, PAR2, 5-HT, CgA and SERT, and reducing CGRP and TNF-α level.
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Hai-Lian
authors.initials: HL
authors.lastname: Shi
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Chu-Hsuan
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Ding
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Fei
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Yuan
authors.affiliation: Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Jian-Qun
authors.initials: JQ
authors.lastname: Xie
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D053379:Chromogranin A / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D011312:Pressure; D016601:RNA-Binding Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053379:Chromogranin A; D004365:Drugs, Chinese Herbal; D016601:RNA-Binding Proteins; D044464:Receptor, PAR-2; C482440:Sert1 protein, rat; D050051:Transient Receptor Potential Channels; D014409:Tumor Necrosis Factor-alpha; C506153:chromogranin A, rat; D012701:Serotonin; D015740:Calcitonin Gene-Related Peptide
keywords: Calcitonin-gene-related peptide; Protease-activated receptor; Serotonin; Serotonin transporter; Shugan decoction; Transient receptor potential; Tumor necrosis factor-α; Visceral hyperalgesia