Motilin receptor explained

Motilin receptor is a G protein-coupled receptor (previously GPCR38)^{[1] [2] [3]} that binds motilin.^{[4] [5]} It was first cloned in 1999 by Merck Laboratories.^[6] and scientists have since been searching for compounds to modify its behavior.^[7]

The primary structure of the motilin receptor consists of 412 amino acids, while its tertiary structure resembles a golf club.^[8] The protein C-terminal protein protects from enzymatic degradation, while the N-terminal is essential for binding.

Function

The primary function of the motilin receptor is to contract gastric smooth muscle during phase III of the migrating motor complex (MMC). In this final phase of the MMC, N-type motilin receptors in the distal antral pump of the stomach are activated.^[9] This causes contraction of the gastric smooth muscle, sieving food into the small intestine, and priming the stomach for the next meal.^[10]

Motilin

Motilin is an intestinal peptide that stimulates the contraction of gastric smooth muscle via the motilin receptor. It is produced by enteroendocrine cells in the proximal small intestine^[11] and secreted cyclically.^[12] Motilin mimetics could be used to increase gastric motility in patients with gastroparesis e.g., constipation-predominant irritable bowel syndrome.^[13] However, none of the candidate drugs that have been tested so far have made it to market.^[14]

Further reading

• Smith RG, Leonard R, Bailey AR, Palyha O, Feighner S, Tan C, Mckee KK, Pong SS, Griffin P, Howard A . 6 . Growth hormone secretagogue receptor family members and ligands . Endocrine . 14 . 1 . 9–14 . February 2001 . 11322507 . 10.1385/ENDO:14:1:009 . 31807893 .
• McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL, Smith RG, Howard AD, Van der Ploeg LH . 6 . Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors . Genomics . 46 . 3 . 426–434 . December 1997 . 9441746 . 10.1006/geno.1997.5069 .
• Feighner SD, Tan CP, McKee KK, Palyha OC, Hreniuk DL, Pong SS, Austin CP, Figueroa D, MacNeil D, Cascieri MA, Nargund R, Bakshi R, Abramovitz M, Stocco R, Kargman S, O'Neill G, Van Der Ploeg LH, Evans J, Patchett AA, Smith RG, Howard AD . 6 . Receptor for motilin identified in the human gastrointestinal system . Science . 284 . 5423 . 2184–2188 . June 1999 . 10381885 . 10.1126/science.284.5423.2184 .
• Miller P, Roy A, St-Pierre S, Dagenais M, Lapointe R, Poitras P . Motilin receptors in the human antrum . American Journal of Physiology. Gastrointestinal and Liver Physiology . 278 . 1 . G18–G23 . January 2000 . 10644557 . 10.1152/ajpgi.2000.278.1.G18 . 41964250 .
• Thielemans L, Depoortere I, Van Assche G, Bender E, Peeters TL . Demonstration of a functional motilin receptor in TE671 cells from human cerebellum . Brain Research . 895 . 1–2 . 119–128 . March 2001 . 11259768 . 10.1016/S0006-8993(01)02055-8 . 19864565 .
• Coulie B, Matsuura B, Dong M, Hadac EM, Pinon DI, Feighner SD, Howard AD, Miller LJ . 6 . Identification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling . The Journal of Biological Chemistry . 276 . 38 . 35518–35522 . September 2001 . 11461914 . 10.1074/jbc.M104489200 . free .
• Thielemans L, Depoortere I, Vanden Broeck J, Peeters TL . The motilin pharmacophore in CHO cells expressing the human motilin receptor . Biochemical and Biophysical Research Communications . 293 . 4 . 1223–1227 . May 2002 . 12054506 . 10.1016/S0006-291X(02)00356-X .
• Depoortere I, Thijs T, Thielemans L, Robberecht P, Peeters TL . Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum . The Journal of Pharmacology and Experimental Therapeutics . 305 . 2 . 660–667 . May 2003 . 12606621 . 10.1124/jpet.102.047563 . 2078474 .
• Matsuura B, Dong M, Naik S, Miller LJ, Onji M . Differential contributions of motilin receptor extracellular domains for peptide and non-peptidyl agonist binding and activity . The Journal of Biological Chemistry . 281 . 18 . 12390–12396 . May 2006 . 16531413 . 10.1074/jbc.M511921200 . free .

External links

• Web site: Motilin Receptors: Motilin . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2007-10-25 . 2011-05-16 . https://web.archive.org/web/20110516084830/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1334 . dead .

Notes and References

1. Book: Gomez GA, Englander EW, Greeley GH . Chapter 7 - Postpyloric Gastrointestinal Peptides . January 2012 . Physiology of the Gastrointestinal Tract . Fifth . 155–198 . Johnson LR, Ghishan FK, Kaunitz JD, Merchant JL . Boston . Academic Press . en . 978-0-12-382026-6 . 10.1016/B978-0-12-382026-6.00007-5 .
2. Web site: Puckrin Z . February 2023 . Everything you need to know about the motilin receptor . 2023-02-24 . www.reprocell.com . en-us.
3. Westaway SM, Sanger GJ . The identification of and rationale for drugs which act at the motilin receptor . Progress in Medicinal Chemistry . 48 . 31–80 . 2009 . 21544957 . 10.1016/s0079-6468(09)04802-4 . 978-0-444-53358-6 .
4. Depoortere I . Motilin and motilin receptors: characterization and functional significance . Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie . 63 . 6 . 511–529 . 2001 . 11813507 .
5. Yang X, Dong L, Yang H . [Evidence for the presence of motilin receptor and a study on the mechanism of motilin induced Ca2+ signaling in rat myenteric neurons] . zh . Sichuan da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition . 37 . 5 . 683–686 . September 2006 . 17037727 .
6. Book: Poitras P . 10.1016/B978-0-12-385095-9.00170-6 . Chapter 170 - Motilin . Handbook of Biologically Active Peptides . 2013 . 1257–1264 . San Diego, CA . Academic Press . 978-0-12-385095-9 . Second.
7. Leming S, Broad J, Cozens SJ, Otterson M, Winchester W, Lee K, Dukes GE, Sanger GJ . 6 . GSK962040: a small molecule motilin receptor agonist which increases gastrointestinal motility in conscious dogs . Neurogastroenterology and Motility . 23 . 10 . 958–e410 . October 2011 . 21895874 . 10.1111/j.1365-2982.2011.01770.x . 21813655 .
8. Book: Kaiya H . Chapter 30 - Ghrelin-motilin family . January 2021 . Handbook of Hormones . Second . 317–319 . Ando H, Ukena K, Nagata S . San Diego . Academic Press . en . 978-0-12-820649-2 . 10.1016/B978-0-12-820649-2.00082-6 . 242138545 .
9. Book: Surjanhata BC, Kuo B . Gastrointestinal Motility and Enteric Neuroscience in Health and Disease . January 2014 . Reference Module in Biomedical Sciences . Elsevier . en . 978-0-12-801238-3 . 10.1016/B978-0-12-801238-3.00051-9 .
10. Book: Taheri S, Ghatei MA, Bloom SR . Chapter 152 - Gastrointestinal Hormones and Tumor Syndromes . January 2010 . 10.1016/B978-1-4160-5583-9.00152-0 . Endocrinology . Sixth . 2759–2773 . Jameson JL, De Groot LJ . Philadelphia . W.B. Saunders . en . 978-1-4160-5583-9 .
11. Book: Vella A . Chapter 38 - Gastrointestinal Hormones and Gut Endocrine Tumors . January 2016 . 10.1016/B978-0-323-29738-7.00038-1 . Williams Textbook of Endocrinology . 1701–1722 . Melmed S, Polonsky KS, Larsen PR, Kronenberg HM . Philadelphia . Elsevier . en . 978-0-323-29738-7 . Thirteenth .
12. Book: Shim J, Yu R . Chapter 7 - Gut Hormones in Pregnancy and Lactation . 2020-01-01 . 10.1016/B978-0-12-814823-5.00007-6 . Maternal-Fetal and Neonatal Endocrinology . 91–99 . Kovacs CS, Deal CL . Academic Press . en . 978-0-12-814823-5 . 208557201 .
13. de Villiers WJ . April 2003 . Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management—2 Volume Set, 7th Edition . Shock . en-US . 19 . 4 . 397–398 . 10.1097/00024382-200304000-00021 . 1540-0514.
14. Book: Lafferty R, O'Harte F, Irwin N, Flatt PR, Gault VA . Pharmacology of Gut Hormone Mimetics for Obesity and Diabetes . https://pure.ulster.ac.uk/en/publications/pharmacology-of-gut-hormone-mimetics-for-obesity-and-diabetes . Reference Module in Biomedical Sciences . 2022 . 301–343 . Elsevier . 10.1016/B978-0-12-820472-6.00035-9 . 978-0-12-820876-2 . 234190503 . 2023-02-24 .