Motilin receptor

Motilin receptor is a G protein-coupled receptor (previously GPCR38)^[3][4][5] that binds motilin.^[6][7] It was first cloned in 1999 by Merck Laboratories.^[8] and scientists have since been searching for compounds to modify its behavior.^[9]

MLNR
Identifiers
Aliases	MLNR, GPR38, MTLR1, motilin receptor
External IDs	OMIM: 602885; HomoloGene: 74398; GeneCards: MLNR; OMA:MLNR - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q14.2 Start 49,220,338 bp[1] End 49,222,377 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle gonad bone marrow fundus body of stomach islet of Langerhans blood stromal cell of endometrium right lobe of thyroid gland kidney n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function growth hormone-releasing hormone receptor activity signal transducer activity G protein-coupled receptor activity G protein-coupled peptide receptor activity hormone binding Cellular component integral component of membrane plasma membrane membrane Biological process G protein-coupled receptor signaling pathway signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2862 n/a Ensembl ENSG00000102539 n/a UniProt O43193 n/a RefSeq (mRNA) NM_001507 n/a RefSeq (protein) NP_001498 n/a Location (UCSC) Chr 13: 49.22 – 49.22 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

The primary structure of the motilin receptor consists of 412 amino acids,^[8] while its tertiary structure resembles a golf club.^[10] The protein C-terminal protein protects from enzymatic degradation, while the N-terminal is essential for binding.^[10]

Function

The primary function of the motilin receptor is to contract gastric smooth muscle during phase III of the migrating motor complex (MMC).^[8] In this final phase of the MMC, N-type motilin receptors in the distal antral pump of the stomach are activated.^[11] This causes contraction of the gastric smooth muscle, sieving food into the small intestine, and priming the stomach for the next meal.^[12]

Motilin

Motilin is an intestinal peptide that stimulates the contraction of gastric smooth muscle via the motilin receptor.^[8] It is produced by enteroendocrine cells in the proximal small intestine^[3][13] and secreted cyclically.^[14] Motilin mimetics could be used to increase gastric motility in patients with gastroparesis e.g., constipation-predominant irritable bowel syndrome.^[15] However, none of the candidate drugs that have been tested so far have made it to market.^[4][16]

References

1. GRCh38: Ensembl release 89: ENSG00000102539 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Gomez GA, Englander EW, Greeley GH (January 2012). "Chapter 7 - Postpyloric Gastrointestinal Peptides". In Johnson LR, Ghishan FK, Kaunitz JD, Merchant JL (eds.). Physiology of the Gastrointestinal Tract (Fifth ed.). Boston: Academic Press. pp. 155–198. doi:10.1016/B978-0-12-382026-6.00007-5. ISBN 978-0-12-382026-6.
4. Puckrin Z (February 2023). "Everything you need to know about the motilin receptor". www.reprocell.com. Retrieved 2023-02-24.
5. Westaway SM, Sanger GJ (2009). "The identification of and rationale for drugs which act at the motilin receptor". Progress in Medicinal Chemistry. 48: 31–80. doi:10.1016/s0079-6468(09)04802-4. ISBN 978-0-444-53358-6. PMID 21544957.
6. Depoortere I (2001). "Motilin and motilin receptors: characterization and functional significance". Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie. 63 (6): 511–529. PMID 11813507.
7. Yang X, Dong L, Yang H (September 2006). "[Evidence for the presence of motilin receptor and a study on the mechanism of motilin induced Ca2+ signaling in rat myenteric neurons]". Sichuan da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition (in Chinese). 37 (5): 683–686. PMID 17037727.
8. Poitras P (2013). "Chapter 170 - Motilin". Handbook of Biologically Active Peptides (Second ed.). San Diego, CA: Academic Press. pp. 1257–1264. doi:10.1016/B978-0-12-385095-9.00170-6. ISBN 978-0-12-385095-9.
9. Leming S, Broad J, Cozens SJ, Otterson M, Winchester W, Lee K, et al. (October 2011). "GSK962040: a small molecule motilin receptor agonist which increases gastrointestinal motility in conscious dogs". Neurogastroenterology and Motility. 23 (10): 958–e410. doi:10.1111/j.1365-2982.2011.01770.x. PMID 21895874. S2CID 21813655.
10. Kaiya H (January 2021). "Chapter 30 - Ghrelin-motilin family". In Ando H, Ukena K, Nagata S (eds.). Handbook of Hormones (Second ed.). San Diego: Academic Press. pp. 317–319. doi:10.1016/B978-0-12-820649-2.00082-6. ISBN 978-0-12-820649-2. S2CID 242138545.
11. Surjanhata BC, Kuo B (January 2014). "Gastrointestinal Motility and Enteric Neuroscience in Health and Disease". Reference Module in Biomedical Sciences. Elsevier. doi:10.1016/B978-0-12-801238-3.00051-9. ISBN 978-0-12-801238-3.
12. Taheri S, Ghatei MA, Bloom SR (January 2010). "Chapter 152 - Gastrointestinal Hormones and Tumor Syndromes". In Jameson JL, De Groot LJ (eds.). Endocrinology (Sixth ed.). Philadelphia: W.B. Saunders. pp. 2759–2773. doi:10.1016/B978-1-4160-5583-9.00152-0. ISBN 978-1-4160-5583-9.
13. Vella A (January 2016). "Chapter 38 - Gastrointestinal Hormones and Gut Endocrine Tumors". In Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (eds.). Williams Textbook of Endocrinology (Thirteenth ed.). Philadelphia: Elsevier. pp. 1701–1722. doi:10.1016/B978-0-323-29738-7.00038-1. ISBN 978-0-323-29738-7.
14. Shim J, Yu R (2020-01-01). "Chapter 7 - Gut Hormones in Pregnancy and Lactation". In Kovacs CS, Deal CL (eds.). Maternal-Fetal and Neonatal Endocrinology. Academic Press. pp. 91–99. doi:10.1016/B978-0-12-814823-5.00007-6. ISBN 978-0-12-814823-5. S2CID 208557201.
15. de Villiers WJ (April 2003). "Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management—2 Volume Set, 7th Edition". Shock. 19 (4): 397–398. doi:10.1097/00024382-200304000-00021. ISSN 1540-0514.
16. Lafferty R, O'Harte F, Irwin N, Flatt PR, Gault VA (2022). "Pharmacology of Gut Hormone Mimetics for Obesity and Diabetes". Reference Module in Biomedical Sciences. Elsevier. pp. 301–343. doi:10.1016/B978-0-12-820472-6.00035-9. ISBN 978-0-12-820876-2. S2CID 234190503. Retrieved 2023-02-24.

Further reading

• Smith RG, Leonard R, Bailey AR, Palyha O, Feighner S, Tan C, et al. (February 2001). "Growth hormone secretagogue receptor family members and ligands". Endocrine. 14 (1): 9–14. doi:10.1385/ENDO:14:1:009. PMID 11322507. S2CID 31807893.
• McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL, et al. (December 1997). "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. doi:10.1006/geno.1997.5069. PMID 9441746.
• Feighner SD, Tan CP, McKee KK, Palyha OC, Hreniuk DL, Pong SS, et al. (June 1999). "Receptor for motilin identified in the human gastrointestinal system". Science. 284 (5423): 2184–2188. doi:10.1126/science.284.5423.2184. PMID 10381885.
• Miller P, Roy A, St-Pierre S, Dagenais M, Lapointe R, Poitras P (January 2000). "Motilin receptors in the human antrum". American Journal of Physiology. Gastrointestinal and Liver Physiology. 278 (1): G18–G23. doi:10.1152/ajpgi.2000.278.1.G18. PMID 10644557. S2CID 41964250.
• Thielemans L, Depoortere I, Van Assche G, Bender E, Peeters TL (March 2001). "Demonstration of a functional motilin receptor in TE671 cells from human cerebellum". Brain Research. 895 (1–2): 119–128. doi:10.1016/S0006-8993(01)02055-8. PMID 11259768. S2CID 19864565.
• Coulie B, Matsuura B, Dong M, Hadac EM, Pinon DI, Feighner SD, et al. (September 2001). "Identification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling". The Journal of Biological Chemistry. 276 (38): 35518–35522. doi:10.1074/jbc.M104489200. PMID 11461914.
• Thielemans L, Depoortere I, Vanden Broeck J, Peeters TL (May 2002). "The motilin pharmacophore in CHO cells expressing the human motilin receptor". Biochemical and Biophysical Research Communications. 293 (4): 1223–1227. doi:10.1016/S0006-291X(02)00356-X. PMID 12054506.
• Depoortere I, Thijs T, Thielemans L, Robberecht P, Peeters TL (May 2003). "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. doi:10.1124/jpet.102.047563. PMID 12606621. S2CID 2078474.
• Matsuura B, Dong M, Naik S, Miller LJ, Onji M (May 2006). "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. doi:10.1074/jbc.M511921200. PMID 16531413.

External links

• "Motilin Receptors: Motilin". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2011-05-16. Retrieved 2007-10-25.
• Motilin+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)