Intraluminal prucalopride increases propulsive motor activities via luminal 5-HT4 receptors in the rabbit colon.

Abstract

Activating luminal 5-HT4 receptors results in the release of 5-HT from enterochromaffin cells into the lamina propria to modulate colonic motility. Our aim was to evaluate characteristics of colonic motor patterns involved in the prokinetic effects of intraluminal prucalopride in the rabbit colon. Colonic motor patterns were studied ex vivo using simultaneous spatiotemporal diameter mapping and pressure sensing. Intraluminal prucalopride and intraluminal exogenous5-HT strongly evoked or enhanced the colonic motor complex at all levels of excitation beginning with generation of clusters of fast propagating contractions (FPCs), then development of long-distance contractions (LDCs) within the clusters, and finally forceful LDCs as the highest level of excitation. Intraluminal prucalopride and intraluminal exogenous5-HT stimulated propulsive motor activity in a dose-dependent and antagonist-sensitive manner by increasing the contraction amplitude, intraluminal pressure, frequency, velocity, and degree of propagation of the colonic motor complex. Activating mucosal 5-HT4 receptors via intraluminal prucalopride or 5-HT increases propulsive motor activity in a graded manner; that is, dependingon starting conditions, amplitudes or frequencies of an activity may increase or a new pattern may be initiated. Our data support further studies into delivering 5-HT4 receptor agonists via colon-targeted drug delivery systems and studies into the role of luminal 5-HT as an essential requirement for normal colon motor pattern generation.