Ghrelin: A new player in the control of gastrointestinal functions

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R), present on pituitary cells secreting growth hormone. Ghrelin and motilin, and GHS-R and the motilin receptor, are structurally related. Surprisingly, ghrelin is most abundant in the stomach, and GHS-R is also present in the stomach and in other organs and tissues, suggesting effects beyond stimulation of growth hormone in the pituitary, and in particular in the regulation of gastrointestinal function. However, as yet ghrelin seems rather a signal by which the digestive system regulates functions other than the digestive process itself. The most important role of ghrelin appears to be stimulation of appetite and regulation of energy homeostasis, favouring adiposity, and thus contributing to obesity. As recently suggested, ghrelin may therefore be called the "saginary" (fattening) peptide. Ghrelin may affect gastric acid secretion and gastroprotection but the suggested role of ghrelin in Helicobacter pylori infection implicates again the saginary effect. Ghrelin is functionally related to motilin as it also stimulates gastrointestinal motility. In rodents, ghrelin may have taken over the function of motilin, as rodents are natural motilin knockouts. Ghrelin appears to be an endocrine signal, possibly reaching the central nervous system via the bloodstream. However, it also uses neural pathways, in particular the vagus. A better understanding of the physiology of ghrelin may lead to new therapeutic approaches in the treatment of obesity and hypomotility syndromes.