title: 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.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tasaka
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Yasunaga
authors.affiliation: Integrated Center for Sciences, Ehime University, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kiyoi
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan. Electronic address: akiki@m.ehime-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, Okayama 703-8516, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suemaru
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Araki
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D009195:Peroxidase / Q000378:metabolism; D000077526:Tropisetron; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000502:physiology*
chemical_list: D016207:Cytokines; D007211:Indoles; D018836:Inflammation Mediators; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D000077526:Tropisetron; D016264:Dextran Sulfate; D009195:Peroxidase; D000157:Aconitine
keywords: Anti-inflammatory; Cholinergic; Macrophage; Ulcerative colitis; α(7) nACh receptor