Motilin is a
hormone released by the endocrine cells of the duodenal mucosa during fasting to stimulate gastrointestinal motility.
Ghrelin, the closest family member of
motilin, was discovered 10 years ago from the rat stomach as the long-awaited endogenous
ligand of the
growth hormone secretagogue receptor.
Ghrelin has now emerged as a multifunctional
hormone with important effects on energy homeostasis but also on gastrointestinal motility. Like
motilin, it induces hunger contractions in the fasting state and acts postprandially to accelerate gastric emptying. While the development of
motilin agonists for the treatment of hypomotility disorders has been going on for more than 15 years, the development of
ghrelin agonists is still in its infancy. The failure of the first generation of
motilin agonists in clinical trials has been largely due to problems of desensitization and worsening of symptoms due to effects on gastric accommodation. These issues are being taken care of with the second generation of
motilin agonists that are currently under evaluation.
Ghrelin agonists have the same potential as
motilin agonists to treat hypomotility disorders but their effects on appetite may even be a bonus to treat disorders such as functional
dyspepsia while
ghrelin's anti-inflammatory effects may make it superior to
motilin to treat post-operative
ileus. Nevertheless the important endocrine activities of
ghrelin may result in side effects which are not encountered with
motilin. Future studies will need to point out whether the
motilin-
ghrelin receptor family will make it as a new class of gastroprokinetics.