Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

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

Language

English

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. © 2009 Elsevier B.V. All rights reserved.

Keywords

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

Publication Date

2009

Source Publication Title

European Journal of Pharmacology

Volume

606

Issue

3-1

Start Page

199

End Page

204

Publisher

Elsevier

DOI

10.1016/j.ejphar.2009.01.031

ISSN (print)

00142999

ISSN (electronic)

18790712

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