Regulation of ingestive behavior, the upper gastrointestinal motility and gastric acid secretion by ghrelin in mammals

Ghrelin, a novel 28-amino acid peptide, was recently identified as the first endogenous ligand for growth-hormone secretagogue receptors (previously known as orphan receptors), and discovered by "reverse, pharmacology". The ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is secreted from X/A cells in gastric oxyntic glands into the blood circulation. Two major molecular forms of ghrelin are found in the stomach and plasma: acyl ghrelin with O-n-octanoylated serine in the position 3, and des-acyl ghrelin. Among dozens of enzymes, hormones and other factors secreted by the gastrointestinal tract response to food in the lumen acyl ghrelin is the only gastrointestinal signal to increase meal size. Acyl ghrelin stimulates food intake both in free-feeding (naturally fed) and food-deprived (fasted) rodents, and induces adiposity. Also, acyl ghrelin ameliorates cancer cachexia in nude-mice, and alleviates ingestive behavior induced by cancer chemotherapy-related dyspepsia in normal rats. However, des-acyl ghrelin counteracts the metabolic but not the neuroendocrine response to acyl ghrelin. Transgenic mice overexpressing des-acyl ghrelin have been shown small phenotype. In addition, des-acyl ghrelin inhibits food intake in food-deprived mice and rats. Acyl ghrelin stimulates gastrointestinal motor activity and accelerates gastric emptying in rats but not in dogs. On the contrary des-acyl ghrelin has been shown to disrupt gastric motility in rats, and delay gastric emptying in mice and rats. For the majority of experiments, acyl ghrelin stimulates gastric acid secretion in rats, however, different results exist.