| Title: | 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 |
| Authors: | Saegusa, Yayoi Browse this author |
| Takeda, Hiroshi Browse this author |
| Muto, Shuichi Browse this author |
| Oridate, Nobuhiko Browse this author |
| Nakagawa, Koji Browse this author |
| Sadakane, Chiharu Browse this author |
| Nahata, Miwa Browse this author |
| Harada, Yumi Browse this author |
| Iizuka, Mizuki Browse this author |
| Hattori, Tomohisa Browse this author |
| Asaka, Masahiro Browse this author |
| Keywords: | acetylcholine |
| gastroesophageal reflux disease |
| lower esophageal sphincter |
| motility |
| rat |
| serotonin |
| Issue Date: | May-2011 |
| Publisher: | Pharmaceutical Society of Japan |
| Journal Title: | Biological & Pharmaceutical Bulletin |
| Volume: | 34 |
| Issue: | 5 |
| Start Page: | 704 |
| End Page: | 711 |
| Publisher DOI: | 10.1248/bpb.34.704 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/45485 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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