Gastrointestinal hormones are peptides released into the portal system to get access to target cells having a specific receptor. Gastrointestinal hormones are an essential part of the digestive system since they regulate smooth muscle contractions of the gastrointestinal system allowing the food to move throughout the gastrointestinal tract. Motilin is the hormone that is responsible for the migrating motor complex (MMC), which is also known as the interdigestive myoelectric complex. The migrating motor complex is vital for activating the smooth muscles of the gastrointestinal tract allowing the undigestible food to move into large intestine in the unfed period. Motilin gets released by the entero-endocrine cells called M cells from the upper small intestine. To date, there is no reported classical clinical syndrome of motilin deficiency or excess. However, motilin is reduced in pregnancy, during which there is gastrointestinal tract hypomotility. Furthermore, the motilin level is sensitive to the food ingested. Motilin levels decrease by ingesting glucose, and ingesting food containing fat stimulates motilin levels. Motilin was discovered as a hormone in 1972.
The gastrointestinal peristalsis is increased hormonally by cholecystokinin, gastrin, serotonin, insulin, and motilin. The gastrointestinal motility is decreased hormonally by glucagon and secretin. The current thinking is that secretin decreases the motility of the digestive tract by reducing the level of plasma motilin.
The gastrointestinal tract has circular and longitudinal muscles. The circular muscle contraction of the digestive tract leads to a decrease in the diameter of the contracted segment in the gastrointestinal tract. The longitudinal muscle contraction casues a reduction of the length of the contracted part in the digestive tract.
Motilin binds to the motilin receptors, which are G protein-coupled receptors. The ligand of the motilin receptor is unknown. The motilin receptors coupled with G-protein that further stimulates phospholipase C which synthesizes inositol-trisphosphate. When the motilin receptors get activated, the smooth muscles get contracted. Motilin works via actions on the enteric neurons, smooth muscle cells, and vagal afferents. Smooth muscle contraction mediation occurs by increased intracellular calcium and diacylglycerol. Motilin has homology with ghrelin and its receptor, but ghrelin does not bind to the motilin receptor.
In the fourth week of pregnancy, the distal part of the foregut and the proximal portion of the midgut form the origin of the duodenum. The junction of the two parts of the duodenum is just distal to the origin of the liver bud.
In the fifth week of the pregnancy, the epithelial cells proliferate, making the duodenal lumen smaller.
The target cells of motilin are large intestine, small intestine, stomach, lower esophageal sphincter, and gallbladder. The expression of the motilin receptor is differential throughout the gastrointestinal tract in dogs, and researchers found that duodenum and ileum have the most robust immunoreactivity to mRNA expression of the motilin receptor.
Motilin acts on the movement of the gastrointestinal tract by regulating the migrating motor complex, called hunger contraction. The migrating motor complex occurs in the fasting, interdigestive periods. The migrating motor complex occurs at 90-minute intervals. The migrating motor complexes facilitate the transportation of the undigested foods, aids bacterial transport from the small intestine into the large intestine, and inhibit the bacterial migration from the large intestine into the terminal ileum. The migrating motor complexes consist of four phases. Phase I is when the smooth muscle of the gastrointestinal tract is quiescent. Phase II is when peristalsis of the smooth muscle of the digestive tract is getting started. Phase III, which is the most characteristic phase of the migrating motor complex, is when the smooth muscle of the gastrointestinal tract rapidly contracts. In phase III, the pylorus of the stomach remains open, allowing undigested food to move into the small intestine. Phase IV is the transition phase between the contraction of phase III and the inactive state of phase I.
Motilin’s primary function is to increase the migrating motor complex. Motilin concentration has no weight correlation. Motilin is considered recently as a primary orexigenic hormone by modulating the neurocircuit in the brain.
Motilin raises pepsin output and the acid secretion in the stomach. The motilin effect in the lower esophageal sphincter is the contraction of the sphincter and increased resting pressure the sphincter. Motilin causes contraction of the stomach and the lower esophageal sphincter, whereas it does not affect the contraction of the esophagus. The level of motilin is directly proportional to the number of the contractions of the stomach and the number of the contractions of the lower esophageal sphincter.
Motilin is released periodically and increased during the fasting period. During the interdigestive period, motility increases water and protein secretion through the pancreas. Motilin secretion is enhanced by the food that contains fat, whereas suppressed by the food that contains glucose. Acidification of the duodenum can increase motilin release.
A study measured motilin levels during pregnancy, and levels of motilin demonstrated significant reduction. The motilin level returned to its average level one week postpartum. This phenomenon can be advanced to explain why pregnant women have gastrointestinal hypomotility partially. Gastrointestinal hypomotility in pregnant women can manifest as constipation, heartburn, and gallbladder stasis.
Erythromycin activates the motilin receptors, which are G protein-coupled receptors. Such compounds have the name motilides. Using erythromycin can cause concentration-dependent contractions of the stomach and promote the gastric emptying significantly. However, erythromycin has less potency compared to motilin. Erythromycin, the motilin receptor agonist, increases the hunger sensation. There is considerable interest in the drug discovery arena on motilides and more importantly, small molecule motilin receptor agonists, given their prokinetic effect; this could usher in more focussed therapies for diabetic gastroparesis, a frustrating complication for patient and physician.
A study examined patients who underwent T tube after choledochotomy and cholecystectomy have duodenal-biliary reflux. The level of motilin was measured in patients after having a T tube after choledochotomy and cholecystectomy. Researchers divided the patients into two groups, which were the reflux group and control group. The level of motilin of reflux group patients had a much lower motilin level compared to the control group. This observation could probably explain the cause of the duodenal-biliary reflux. The lower level of motilin causes hypomotility of the sphincter of Oddi.
|||Mitznegg P,Bloom SR,Domschke W,Haecki WH,Domschke S,Belohlavek D,Wünsch E,Demling L, Effect of secretin on plasma motilin in man. Gut. 1977 Jun; [PubMed PMID: 17563]|
|||Kitazawa T,Kaiya H, Regulation of Gastrointestinal Motility by Motilin and Ghrelin in Vertebrates. Frontiers in endocrinology. 2019; [PubMed PMID: 31156548]|
|||Kato S,Takahashi A,Shindo M,Yoshida A,Kawamura T,Matsumoto K,Matsuura B, Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice. PloS one. 2019; [PubMed PMID: 30789939]|
|||Christofides ND,Ghatei MA,Bloom SR,Borberg C,Gillmer MD, Decreased plasma motilin concentrations in pregnancy. British medical journal (Clinical research ed.). 1982 Nov 20; [PubMed PMID: 6814598]|
|||He Y,Wang H,Yang D,Wang C,Yang L,Jin C, Differential expression of motilin receptor in various parts of gastrointestinal tract in dogs. Gastroenterology research and practice. 2015; [PubMed PMID: 25918525]|
|||Zhao D,Meyer-Gerspach AC,Deloose E,Iven J,Weltens N,Depoortere I,O'daly O,Tack J,Van Oudenhove L, The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study. Scientific reports. 2018 Jan 29; [PubMed PMID: 29379095]|
|||Deloose E,Janssen P,Depoortere I,Tack J, The migrating motor complex: control mechanisms and its role in health and disease. Nature reviews. Gastroenterology [PubMed PMID: 22450306]|
|||Konturek SJ,Dembinski A,Krol R,Wünsch E, Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs. The Journal of physiology. 1977 Jan; [PubMed PMID: 321755]|
|||Meissner AJ,Bowes KL,Zwick R,Daniel EE, Effect of motilin on the lower oesophageal sphincter. Gut. 1976 Dec; [PubMed PMID: 1017712]|
|||Korimilli A,Parkman HP, Effect of atilmotin, a motilin receptor agonist, on esophageal, lower esophageal sphincter, and gastric pressures. Digestive diseases and sciences. 2010 Feb; [PubMed PMID: 19997977]|
|||Magee DF,Naruse S, The role of motilin in periodic interdigestive pancreatic secretion in dogs. The Journal of physiology. 1984 Oct; [PubMed PMID: 6491998]|
|||Christofides ND,Bloom SR,Besterman HS,Adrian TE,Ghatei MA, Release of motilin by oral and intravenous nutrients in man. Gut. 1979 Feb; [PubMed PMID: 428820]|
|||Modlin IM,Mitznegg P,Bloom SR, Motilin release in the pig. Gut. 1978 May; [PubMed PMID: 658771]|
|||Zhang ZH,Wu SD,Wang B,Su Y,Jin JZ,Kong J,Wang HL, Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux, plasma motilin and serum gastrin. World journal of gastroenterology. 2008 Jul 7; [PubMed PMID: 18609694]|
|||Deloose E,Verbeure W,Depoortere I,Tack J, Motilin: from gastric motility stimulation to hunger signalling. Nature reviews. Endocrinology. 2019 Apr [PubMed PMID: 30675023]|