title: Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model.
abstract: BACKGROUND
  Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice.
  
  
  METHODS
  Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress.
  
  
  RESULTS
  Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist.
  
  
  CONCLUSIONS
  Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nahata
authors.forename: Y
authors.initials: Y
authors.lastname: Saegusa
authors.forename: C
authors.initials: C
authors.lastname: Sadakane
authors.forename: C
authors.initials: C
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: N
authors.initials: N
authors.lastname: Okubo
authors.forename: S
authors.initials: S
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005767:Gastrointestinal Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019518:Postprandial Period / Q000187:drug effects*; D013315:Stress, Psychological / Q000097:blood / Q000150:complications*
chemical_list: D004365:Drugs, Chinese Herbal; D054439:Ghrelin; C422650:ghrelin, des-n-octanoyl; C084136:liu-jun-zi-tang
keywords: acylated ghrelin; des-acyl ghrelin; dysmotility; gastric emptying; restraint stress; rikkunshito