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.