title: Ghrelin and motilin receptors as drug targets for gastrointestinal disorders.
abstract: The gastrointestinal tract is the major source of the related hormones ghrelin and motilin, which act on structurally similar G protein-coupled receptors. Nevertheless, selective receptor agonists are available. The primary roles of endogenous ghrelin and motilin in the digestive system are to increase appetite or hedonic eating (ghrelin) and initiate phase III of gastric migrating myoelectric complexes (motilin). Ghrelin and motilin also both inhibit nausea. In clinical trials, the motilin receptor agonist camicinal increased gastric emptying, but at lower doses reduced gastroparesis symptoms and improved appetite. Ghrelin receptor agonists have been trialled for the treatment of diabetic gastroparesis because of their ability to increase gastric emptying, but with mixed results; however, relamorelin, a ghrelin agonist, reduced nausea and vomiting in patients with this disorder. Treatment of postoperative ileus with a ghrelin receptor agonist proved unsuccessful. Centrally penetrant ghrelin receptor agonists stimulate defecation in animals and humans, although ghrelin itself does not seem to control colorectal function. Thus, the most promising uses of motilin receptor agonists are the treatment of gastroparesis or conditions with slow gastric emptying, and ghrelin receptor agonists hold potential for the reduction of nausea and vomiting, and the treatment of constipation. Therapeutic, gastrointestinal roles for receptor antagonists or inverse agonists have not been identified.
authors.affiliation: National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 1st Floor, Abernethy Building, 2 Newark Street, London E1 2AT, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Sanger
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, VIC 3010, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D001066:Appetite / Q000187:drug effects / Q000502:physiology; D003248:Constipation / Q000188:drug therapy / Q000503:physiopathology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000502:physiology; D006801:Humans; D006815:Hunger / Q000187:drug effects / Q000502:physiology; D009037:Motilin / Q000502:physiology; D009325:Nausea / Q000188:drug therapy / Q000503:physiopathology; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000187:drug effects* / Q000502:physiology; D054440:Receptors, Ghrelin / Q000819:agonists / Q000187:drug effects* / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005765:Gastrointestinal Agents; D054439:Ghrelin; D011964:Receptors, Gastrointestinal Hormone; D054440:Receptors, Ghrelin; D018013:Receptors, Neuropeptide; C422650:ghrelin, des-n-octanoyl; C050802:motilin receptor; D009037:Motilin