title: Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus.
abstract: BACKGROUND
  Delayed gastric emptying is a common disorder with few effective therapeutic options. The goal of this study was to investigate whether ipamorelin, a synthetic peptidomimetic that acts on the ghrelin receptor, accelerates gastric emptying in a rodent model of gastroparesis induced by abdominal surgery and intestinal manipulation.
  
  
  METHODS
  Fasted adult male rats were subjected to laparotomy and intestinal manipulation. Following the surgery rats received ipamorelin (0.014-0.14 µmol/kg) or vehicle control via intravenous administration. Gastric emptying was measured by the percent of total recovered radioactivity remaining in the stomach 15 minutes after intragastric gavage of 1.5 mL of (99m)Tc (technicium-99m) sulfur colloid in 0.5% methylcellulose. In a separate group of rats subjected to laparotomy and intestinal manipulation, the gastric fundus was isolated and tissue segments were suspended in an organ bath to assess the effect of ipamorelin (1 µM) on gastric smooth muscle contractility induced by acetylcholine and electrical field stimulation.
  
  
  RESULTS
  Abdominal surgery caused a delay in gastric emptying with 78% ± 5% of the meal remaining in the stomach in vehicle controls. Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%. Following abdominal surgery and intestinal manipulation, isolated preparations of gastric smooth muscle exhibited a marked inhibition of acetylcholine and electrical field stimulation-induced contractile responses, which were reversed by ipamorelin and ghrelin.
  
  
  CONCLUSIONS
  These results suggest that ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.
authors.affiliation: VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Greenwood-Van Meerveld
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Tyler
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Mohammadi
authors.affiliation: Helsinn Healthcare SA, Lugano, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pietra
keywords: gastroparesis; ipamorelin; rat; stomach