Involvement of stimulation of α7 nicotinic acetylcholine receptors in the suppressive effect of tropisetron on dextran sulfate sodium-induced colitis in mice.

Abstract

Ulcerative colitis (UC) involves chronic inflammation of the large intestine. Several agents are used to treat UC, but adverse side effects are remaining problems. We examined the effect of tropisetron as a new type of drug for UC using a dextran sulfate sodium (DSS)-induced model of colitis in mice. We developed a DSS-induced model of colitis and calculated the Disease Activity Index and colon length. We measured myeloperoxidase activity and determined the protein level and mRNA level of cytokines in the colon. DSS-induced colitis was ameliorated by administration of tropisetron and PNU282987. Pre-administration of methyllycaconitine diminished the suppressive effect of tropisetron upon DSS-induced colitis. These findings suggested that α7 nicotinic acetylcholine receptors (α7 nAChRs) were related to the suppressive effect of tropisetron on DSS-induced colitis. Additionally, stimulation of α7 nAChRs decreased the colon level of interleukin-6 and interferon-γ upon DSS administration. Furthermore, stimulation of α7 nAChRs decreased macrophage infiltration, with expression of α7 nAChR increased by DSS administration. These results suggest that the underlying mechanism of this suppressive effect on DSS-induced colitis is via stimulation of α7 nAChRs and involves suppression of expression of pro-inflammatory cytokines. Tropisetron could be a new type of therapeutic agent for UC.

• Authors: Yuichi Tasaka, Daiki Yasunaga, Takeshi Kiyoi, Mamoru Tanaka, Akihiro Tanaka, Katsuya Suemaru, Hiroaki Araki
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 127 Issue 3 Pg. 275-83 (Mar 2015) ISSN: 1347-8648 [Electronic] Japan
• PMID: 25837923 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Indoles
• Inflammation Mediators
• alpha7 Nicotinic Acetylcholine Receptor
• methyllycaconitine
• Tropisetron
• Dextran Sulfate
• Peroxidase
• Aconitine

Topics

• Aconitine (analogs & derivatives, pharmacology)
• Animals
• Colitis (chemically induced, drug therapy, genetics, metabolism)
• Colitis, Ulcerative (chemically induced, drug therapy, genetics, metabolism)
• Colon (metabolism)
• Cytokines (metabolism)
• Dextran Sulfate
• Disease Models, Animal
• Indoles (antagonists & inhibitors, pharmacology, therapeutic use)
• Inflammation Mediators (metabolism)
• Male
• Mice, Inbred ICR
• Peroxidase (metabolism)
• Tropisetron
• alpha7 Nicotinic Acetylcholine Receptor (physiology)