Role of New Appetite Hormones Ghrelin, Orexin-A and Obestatin in the Mechanism of Healing of Chronic Gastric Ulcers

The regulation of appetite is regulated by complex mechanism involving brain-gut axis and hormonal and non-hormonal factors acting through the activity of satiety and hunger centers located in the hypothalamus [Wren & Bloom, 2007]. Among hormones controlling appetite are gastrointestinal hormones such as cholecystokinin, PYY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomedulin, the endocrine pancreatic hormones including insulin and glucagon and endocannabinoids [Wren &Bloom, 2007]. Recent discoveries of ghrelin and orexin-A gave a new insight into the understanding of mechanism of appetite control, satiety and obesity. Ghrelin is a novel 28-amino acid peptide that has recently been discovered in rat and human gastrointestinal tract, particularly in gastric mucosa, as an endogenous ligand for growth hormone (GH) secretagogue receptor (GHS-R) [Kojima et al., 1999]. Ghrelin stimulates food intake and body weight gain exerting a modulating effect on energy expenditure acting through afferent nerves and directly on hypothalamic feeding centers [Kojima et al., 1999; Tomasetto et al., 2000]. This peptide was also shown to enhance the gastric motility and gastric secretion [Tschop et al., 2000; Date et al., 2001]. Ghrelin is considered as an orexigenic peptide produced by the stomach, acting as a meal initiator [Masuda et al., 2000; Ariyasu et al., 2001]. Little is known about other factors that might affect ghrelin secretion in the stomach and its influence on gastrointestinal integrity has not been fully elucidated. A recent study in humans revealed that stomach is a major source of circulating ghrelin and that gastrectomy produced dramatic fall in the plasma ghrelin levels, whereas fasting and anorexia nervosa was accompanied by elevated plasma ghrelin levels [Ariyasu et al., 2001]. The orexins also called hypocretins, are neuropeptides novel originally discovered in a small group of neurons in the hypothalamic area (LHA) [Sakurai et al., 1998; de Lecea et al., 1998]. identified two peptides that were endogenous ligands to orphan receptor HFGAN72 [Sakurai et al., 1998]. They found that these peptides after i.c.v. injection stimulated food