Intracolonical administration of protease-activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats

Zhi Li, Xiao Jun Zhang, Hong xi Xu, Joseph J.Y. Sung, Zhaoxiang BIAN*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

10 Citations (Scopus)

Abstract

This study aimed to investigate the underlying mechanism of protease-activated receptor-2 (PAR-2) agonist-induced visceral hyperalgesia. Male Sprague-Dawley rat pups were submitted to colonic injection of PAR-2 agonist for 6 consecutive days. The visceral sensitivity to colorectal distention was evaluated by electromyography. The enterochromaffin (EC) cell number, 5-HT content and tryrptophan hydroxylase (TPH) protein expression were detected with immunohistochemistry, fluorescent measurement and Western blot analysis. PAR-2 agonist induced a significant increase of visceral nociceptive response to colorectal distention and a series of neurochemical changes in rat colon, including proliferation of EC cells, increased 5-HT content and enhanced TPH expression. Expression of PAR-2 in EC cells was reported for the first time. Further, selective 5-HT3 receptor antagonist alosteron significantly inhibited PAR-2-induced visceral hyperalgesia. The enhanced 5-HT signaling is likely responsible for the visceral hyperalgesia induced by PAR-2 agonist. Interruption of this pathway is a possible target for the treatment of visceral hyperalgesia in gastrointestinal diseases.

Original languageEnglish
Pages (from-to)199-204
Number of pages6
JournalEuropean Journal of Pharmacology
Volume606
Issue number1-3
DOIs
Publication statusPublished - 15 Mar 2009

Scopus Subject Areas

  • Pharmacology

User-Defined Keywords

  • 5-HT
  • EC cell
  • PAR-2
  • Protease-activated receptor (PAR)
  • Serotonin
  • Visceral hyperalgesia

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