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.
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-HT(4) 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-HT(4) 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-HT(4)-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.
authors.affiliation: Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Saegusa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Muto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Oridate
authors.forename: Koji
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sadakane
authors.forename: Miwa
authors.initials: M
authors.lastname: Nahata
authors.forename: Yumi
authors.initials: Y
authors.lastname: Harada
authors.forename: Mizuki
authors.initials: M
authors.lastname: Iizuka
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D049630:Esophageal Sphincter, Lower / Q000378:metabolism / Q000503:physiopathology*; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D012701:Serotonin; D000109:Acetylcholine