Ghrelin and the gut.

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) which was identified in the pituitary gland and is now named the ghrelin receptor. However, the peptide is most abundant in the stomach and ghrelin receptors are present in all major organ systems and tissues. Ghrelin forms with motilin, a new gut peptide family and the sequence similarities of peptides and receptors suggest they evolved by gene duplication. Nevertheless, no cross-reactivity exits between both peptides. Ghrelin shares with motilin motor effects in the gut, in particular gastric emptying and the induction of the migrating motor complex, but ghrelin also affects gastric acid secretion, offers gastroprotection and may modulate intestinal inflammation. The effects of ghrelin result from the activation of central, vagal and enteric neural receptors and receptors on immune cells. Ghrelin agonists have been developed for the treatment of hypomotility disorders and the peptidomimetic TZP-102 is in phase 2 clinical trials for diabetic gastroparesis.