The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin

BackgroundDiscovery 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. MethodsAnesthetized rats were used to investigate sites and mechanisms of action of ulimorelin. Key ResultsIntravenous ulimorelin (1-5mg/kg) caused a substantial and prolonged (similar to 1h) 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 (5g) to the lumbosacral spinal cord. Conclusions & InferencesUlimorelin 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.