Decreased Motility of the Lower Esophageal Sphincter in a Rat Model of Gastroesophageal Reflux Disease May Be Mediated by Reductions of Serotonin and Acetylcholine Signaling

Saegusa, Yayoi; Takeda, Hiroshi; Muto, Shuichi et al.

Biological & Pharmaceutical Bulletin, 2011, 34(5), 704-711

Permalink : https://hdl.handle.net/2115/45485

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アクセス権
open access
URI
https://hdl.handle.net/2115/45485
タイトル
Decreased Motility of the Lower Esophageal Sphincter in a Rat Model of Gastroesophageal Reflux Disease May Be Mediated by Reductions of Serotonin and Acetylcholine Signaling
著者
Saegusa, Yayoi ; Takeda, Hiroshi ; Muto, Shuichi ; Oridate, Nobuhiko ; Nakagawa, Koji ; Sadakane, Chiharu ; Nahata, Miwa ; Harada, Yumi ; Iizuka, Mizuki ; Hattori, Tomohisa ; Asaka, Masahiro
著者名
Saegusa, Yayoi
著者名
Takeda, Hiroshi
著者名
Muto, Shuichi
著者名
Oridate, Nobuhiko
著者名
Nakagawa, Koji
著者名
Sadakane, Chiharu
著者名
Nahata, Miwa
著者名
Harada, Yumi
著者名
Iizuka, Mizuki
著者名
Hattori, Tomohisa
著者名
Asaka, Masahiro
言語
英語
キーワード
acetylcholine
gastroesophageal reflux disease
lower esophageal sphincter
motility
rat
serotonin
発行日
2011-05
出版者
Pharmaceutical Society of Japan
収録物名
Biological & Pharmaceutical Bulletin
巻(号)
34(5)
ページ
704-711
抄録
To elucidate the altered function of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD), we evaluated the motility proximal to LES using force transducers, contraction and relaxation responses to neurotransmitters in LES strips, and gene expression of neurotransmitter receptors in GERD rats. Force transducers were applied to the proximal LES, and contraction of the LES was monitored during free moving. In addition, LES was isolated from sham-operated and GERD rats to investigate the LES function in an organ bath, and to determine gene expression. The in vivo motility proximal to LES (% motility index) in conscious rats was decreased by atropine treatment and increased by cisapride (5-HT4 receptor agonist) treatment. Acetylcholine- and serotonin (5-HT)-induced LES contraction and sodium nitroprusside-induced relaxation in LES strips of GERD rats markedly decreased compared to sham-operated rats. The mRNA expressions of 5-HT4 and muscarinic acetylcholine 3 receptors were significantly reduced in esophageal LES strips of GERD rats compared with sham-operated rats. Intraperitoneal administration of cisapride improves the erosive damage in the esophagus in GERD rats. It is suggested that the reduction of 5-HT-induced contraction in LES strips in GERD rats may be partly due to the decrease in 5-HT4-receptor activation. The reduction of LES function may be due to the decrease in neurotransmitters signal transduction, leading to the deterioration of histopathological damage in GERD.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
PISSN
0918-6158
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1248/bpb.34.704