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The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin
journal contribution
posted on 2014-02-01, 00:00 authored by R V Pustovit, B Callaghan, S Kosari, Leni RiveraLeni Rivera, H Thomas, J A Brock, J B FurnessBACKGROUND: 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. KEY 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 & INFERENCES: 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.
History
Journal
Neurogastroenterology and motilityVolume
26Issue
2Pagination
264 - 271Publisher
Wiley-BlackwellLocation
Chichester, Eng.Publisher DOI
eISSN
1365-2982Language
engPublication classification
C Journal article; C1.1 Refereed article in a scholarly journalCopyright notice
2013, Wiley-BlackwellUsage metrics
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No categories selectedKeywords
defecationghrelinghrelin receptorsAnimalsColonInjections, SpinalMacrocyclic CompoundsMaleRatsRats, Sprague-DawleyReceptors, GhrelinRectumSpinal CordScience & TechnologyLife Sciences & BiomedicineGastroenterology & HepatologyClinical NeurologyNeurosciencesNeurosciences & NeurologyDES-ACYL GHRELINCOLORECTAL MOTILITYGROWTHCONSTIPATIONSTIMULATIONNEURONSANTAGONISTSTHERAPIESPATHWAYSARTICLE
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