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
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概要
- 論文の詳細を見る
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.
著者
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TAKEDA Hiroshi
Department of Medical Information Science, Osaka University Graduate School of Medicine
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Nakagawa Koji
Department of Cardiology, Okayama University School of Medicine
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Asaka Masahiro
Department Of Gastroenterology And Hematology Hokkaido University Graduate School Of Medicine
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Asaka M
Hokkaido Univ. Graduate School Of Medicine Sapporo Jpn
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HATTORI Tomohisa
Tsumura and Co., Pharmacology Research Department, R&D Division
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Hattori Tomohisa
Tsumura & Co. Tsumura Res. Laboratories
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Takeda Hiroshi
Department Of Earth And Planetary Science The University Of Tokyo
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Saegusa Yayoi
Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutica
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Muto Shuichi
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine
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Oridate Nobuhiko
Gastroenterology, Tomakomai City General Hospital
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Sadakane Chiharu
Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutica
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Nahata Miwa
Tsumura Research Laboratories, Tsumura & Co.
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Harada Yumi
Tsumura Research Laboratories, Tsumura & Co.
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Iizuka Mizuki
Tsumura Research Laboratories, Tsumura & Co.
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Nakagawa Koji
Department Of Cardiology Okayama University
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Sadakane Chiharu
Tsumura Research Laboratories Tsumura & Co.
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Takeda Hiroshi
Division Of Pharmasciences Department Of Pathophysiology And Therapeutics Faculty Of Pharmaceutical
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Takeda Hiroshi
Department Of Abdominal Surgery Tenri Hospital
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Asaka Masahiro
Department Of Cancer Preventive Medicine Graduate School Of Medicine Hokkaido University
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Hattori Tomohisa
Tsumura Research Laboratories, Tsumura & Co.
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Harada Yumi
Tsumura Research Laboratories, Tsumura & Co.
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Nahata Miwa
Tsumura Research Laboratories, Tsumura & Co.
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Nakagawa Koji
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University
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