title: The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin.
abstract: BACKGROUND
  Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action.
  
  
  METHODS
  Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin.
  
  
  RESULTS
  Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 μg) to the lumbosacral spinal cord.
  
  
  CONCLUSIONS
  Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville, VIC, Australia.
authors.forename: R V
authors.initials: RV
authors.lastname: Pustovit
authors.forename: B
authors.initials: B
authors.lastname: Callaghan
authors.forename: S
authors.initials: S
authors.lastname: Kosari
authors.forename: L R
authors.initials: LR
authors.lastname: Rivera
authors.forename: H
authors.initials: H
authors.lastname: Thomas
authors.forename: J A
authors.initials: JA
authors.lastname: Brock
authors.forename: J B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D003672:Defecation / Q000187:drug effects*; D007278:Injections, Spinal; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000819:agonists*; D012007:Rectum / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
chemical_list: D047028:Macrocyclic Compounds; D054440:Receptors, Ghrelin; C528884:ulimorelin
keywords: defecation; ghrelin; ghrelin receptors