characteristic of a large object. Stimulus How the secretion of motilin is regulated is largely unknown, although some studies suggest that an alkaline pH in the duodenum stimulates its release. However, at low pH it inhibits gastric motor activity, whereas at high pH it has a stimulatory effect. Some studies in dogs have shown that motilin is released during fasting or interdigestive period, and intake of food during this period can prevent the secretion of motilin. Intravenous injection of glucose, which increases the release of insulin, is also found to inhibit cyclic elevation of plasma motilin. Other studies on dogs have also suggested that motilin acted as endogenous ligand in positive feedback mechanism to stimulate the release of more motilin. In dogs and cats, motilin secretion is stimulated by hydrogen ions (protons) and lipids when the animal is in a "fed" state. Hoever, during fasting, motilin is periodically released into the serum to initiate phase III of the migrating motor complex. Function The main function of motilin is to increase the migrating myoelectric complex component of gastrointestinal motility and stimulate the production of pepsin. Motilin is also called "housekeeper of the gut" because it improves peristalsis in the small intestine and clears out the gut to prepare for the next meal. A high level of motilin secreted between meals into the blood stimulates the contraction of the fundus and antrum and accelerates gastric emptying. It then contracts the gallbladder and increases the squeeze pressure of the lower esophageal sphincter. Other functions of motilin include increasing the release of pancreatic polypeptide and somatostatin. Motilin agonists Erythromycin and related antibiotics act as non-peptide motilin agonists, and are sometimes used for their ability to stimulate gastrointestinal motility. In the case of erythromycin, it is its hemiketal intermediate, formed after an oral dose in the low-pH environment of the stomach lumen, which directly acts on the motilin receptor. Administration of a low dose of erythromycin will induce peristalsis, which provides additional support for the conclusion that motilin secretion triggers this pattern of gastrointestinal motility, rather than results from it. However, some of erythromycin's properties, including antibiotic activity, are not appropriate for a drug designed for chronic use over a patient's lifetime. New motilin agonists are erythromycin-based; however, it may be that this class of drugs becomes redundant. Growth hormone secretagogue receptors share 52% of their DNA with motilin receptors, and agonists of these receptors,