Alterations in serotonin, transient receptor potential channels and protease-activated receptors in rats with irritable bowel syndrome attenuated by Shugan decoction

World J Gastroenterol. 2015 Apr 28;21(16):4852-63. doi: 10.3748/wjg.v21.i16.4852.

Abstract

Aim: 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.

Conclusion: 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.

Keywords: Calcitonin-gene-related peptide; Protease-activated receptor; Serotonin; Serotonin transporter; Shugan decoction; Transient receptor potential; Tumor necrosis factor-α; Visceral hyperalgesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Chromogranin A / metabolism
  • Colon / drug effects*
  • Colon / innervation
  • Colon / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Gastrointestinal Motility / drug effects*
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / innervation
  • Intestinal Mucosa / metabolism
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / metabolism
  • Irritable Bowel Syndrome / physiopathology
  • Male
  • Pain Threshold / drug effects
  • Pressure
  • RNA-Binding Proteins / metabolism
  • Rats, Sprague-Dawley
  • Receptor, PAR-2 / drug effects*
  • Receptor, PAR-2 / metabolism
  • Serotonin / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Transient Receptor Potential Channels / drug effects*
  • Transient Receptor Potential Channels / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chromogranin A
  • Drugs, Chinese Herbal
  • RNA-Binding Proteins
  • Receptor, PAR-2
  • Sert1 protein, rat
  • Transient Receptor Potential Channels
  • Tumor Necrosis Factor-alpha
  • chromogranin A, rat
  • Serotonin
  • Calcitonin Gene-Related Peptide