Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity.
Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.
Ohashi
Katsuyo
K
Discovery Research, Pfizer Global Research and Development, Nagoya Laboratories, Aichi, Japan.
Sato
Yasushi
Y
Iwata
Hiroshi
H
Kawai
Mitsuhisa
M
Kurebayashi
Yoichi
Y
D000818:Animals; D003106:Colon / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D043183:Irritable Bowel Syndrome / Q000139:chemically induced*; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013892:Thioxanthenes / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*; D044004:Xanthones / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D013892:Thioxanthenes; D044004:Xanthones; D014302:Trinitrobenzenesulfonic Acid; C010134:doxantrazole