Intraluminal Prucalopride Increases Propulsive Motor Activities in the Human Colon

Abstract

ABSTRACTBackgroundLuminal application of 5-HT4 receptor agonists can increase peristalsis in the guinea pig, mouse, rat and rabbit colon. Our aim in the present study was to test the effects of intraluminal prucalopride on motor patterns in the human colon.MethodsColonic motor patterns were studied in vivo in a healthy volunteer using High-Resolution Colonic Manometry (HRCM) with an 84-sensor water perfused catheter with 1cm spacing. 5-HT and 5-HT4 receptor immunohistochemistry was performed on human tissue biopsies throughout the colon.Key resultsActivating mucosal 5-HT4 receptors via intraluminal prucalopride enhanced propulsive motor activity in the human colon by increasing occurrence and amplitude of propulsive motor patterns including high-amplitude propagating pressure waves (HAPWs), pancolonic simultaneous pressure waves (SPWs) and HAPW-SPWs. Prucalopride-induced motor patterns had a close temporal association with a significant degree of anal sphincter relaxation and some were accompanied by a strong urge to defecate. Biopsies showed 100% colocalization of the 5-HT4 receptor to enterochromaffin cells throughout the colon and rectum.Conclusions and inferencesActivating luminal 5-HT4 receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity. 5-HT4 receptors were found only on enterochromaffin cells and not ubiquitous on all epithelial cells. Our data support incorporation of prucalopride in colon-specific drug delivery systems as a prokinetic to treat colonic hypomotility disorders.50 word abstractHigh-resolution colonic manometry and biopsy immunohistochemistry revealed that 5-HT4 receptors in the lumen of the human colon are present exclusively on enterochromaffin cells and that the 5-HT4 agonist prucalopride evokes all major propulsive motor patterns, associated with significant anal sphincter relaxation, when given intraluminally.250-character clinical messageActivating luminal 5-HT4 receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity in the human colon. Colon-specific delivery systems with a 5-HT4 agonist may become the preferred colon prokinetic.