Intracolonical administration of protease-activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats.
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-HT(3) 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.
Li
Zhi
Z
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Zhang
Xiao-Jun
XJ
Xu
Hong-xi
HX
Sung
Joseph J Y
JJ
Bian
Zhao-xiang
ZX
D000595:Amino Acid Sequence; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D002452:Cell Count; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism / Q000628:therapy; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D002243:Carbolines; D009842:Oligopeptides; D044464:Receptor, PAR-2; C090840:alosetron; D012701:Serotonin; D014365:Tryptophan Hydroxylase