title: Ghrelin enhancer, rikkunshito, improves postprandial gastric motor dysfunction in an experimental stress model.
abstract: BACKGROUND
  Functional dyspepsia (FD) is one of the most common disorders of gastrointestinal (GI) diseases. However, no curable treatment is available for FD because the detailed mechanism of GI dysfunction in stressed conditions remains unclear. We aimed to clarify the association between endogenous acylated ghrelin signaling and gastric motor dysfunction and explore the possibility of a drug with ghrelin signal-enhancing action for FD treatment.
  
  
  METHODS
  Solid gastric emptying (GE) and plasma acylated ghrelin levels were evaluated in an urocortin1 (UCN1) -induced stress model. To clarify the role of acylated ghrelin on GI dysfunction in the model, exogenous acylated ghrelin, an endogenous ghrelin enhancer, rikkunshito, or an α2 -adrenergic receptor (AR) antagonist was administered. Postprandial motor function was investigated using a strain gauge force transducer in a free-moving condition.
  
  
  RESULTS
  Exogenous acylated ghrelin supplementation restored UCN1-induced delayed GE. Alpha2 -AR antagonist and rikkunshito inhibited the reduction in plasma acylated ghrelin and GE in the stress model. The action of rikkunshito on delayed GE was blocked by co-administration of the ghrelin receptor antagonist. UCN1 decreased the amplitude of contraction in the antrum while increasing it in the duodenum. The motility index of the antrum but not the duodenum was significantly reduced by UCN1 treatment, which was improved by acylated ghrelin or rikkunshito.
  
  
  CONCLUSIONS
  The UCN1-induced gastric motility dysfunction was mediated by abnormal acylated ghrelin dynamics. Supplementation of exogenous acylated ghrelin or enhancement of endogenous acylated ghrelin secretion by rikkunshito may be effective in treating functional GI disorders.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.|Central Research Laboratories, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ro
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ochiai
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Hosomi
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Fujitsuka
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yakabi
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005746:Gastric Emptying / Q000187:drug effects*; D005767:Gastrointestinal Diseases / Q000150:complications / Q000517:prevention & control*; D054439:Ghrelin / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D019518:Postprandial Period / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000139:chemically induced / Q000150:complications*; D054832:Urocortins; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D004365:Drugs, Chinese Herbal; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D054832:Urocortins; C084136:liu-jun-zi-tang; D015016:Yohimbine
keywords: acylated ghrelin; gastric dysfunction; rikkunshito; stress; urocortin1; α2-adrenergic receptor