Mechanism of Action of Intraluminal Prucalopride
It is likely that intraluminal prucalopride induces propulsive motor patterns in humans by a sequence of events that start with 5-HT release from enterochromaffin cells leading to activation of mucosal endings of IPANs which communicate with neurons in the myenteric plexus. IPANs and vagal and pelvic afferent endings come into close proximity to the mucosal epithelium (50) (36) (18) which exposes them to chemicals released from enterochromaffin cells. Subsequently, propagation of excitation along the colon occurs through myenteric neuronal pathways in concert with myenteric ICC to activate longitudinal and circular muscles.
It has been suggested that the 5-HT4R is ubiquitously expressed by all epithelial cells in the murine colon. This was based on photomicrograph data from colonic sections of a 5-HT4R(BAC)-eGFP transgenic mouse in which cells express the 5-HT4R green fluorescent signal (36). In contrast, our data using immunohistochemistry revealed 100% co-expression of 5-HT and 5HT4R in human colonic epithelium throughout the colon, suggesting that enterochromaffin cells are the only epithelial cells expressing 5HT4Rs in the human colon. It is therefore likely that luminal prucalopride acts on these 5-HT4Rs.