View source for Motilin

{{Pfam_box
| Symbol = Motilin_ghrelin
| Name = Motilin/ghrelin
| image = PDB 1lbj EBI.jpg
| width =
| caption = Structure of motilin in isotropic phospholipid bicellar solution.<ref name="pmid12495026"/>
| Pfam= PF04644
| InterPro= IPR006738
| SMART=
| Prosite =
| SCOP = 1lbj
| TCDB =
| OPM family=145
| OPM protein= 1lbj
| PDB= 
}}
{{Infobox protein
   |Name=Motilin
   |image=Motilin_Image.png
   |caption= NMR solution structure of motilin in phospholipid bicellar solution.<ref name="pmid12495026">{{PDB|1lbj}}; {{cite journal | vauthors = Andersson A, Mäler L | title = NMR solution structure and dynamics of motilin in isotropic phospholipid bicellar solution | journal = Journal of Biomolecular NMR | volume = 24 | issue = 2 | pages = 103–12 | date = October 2002 | pmid = 12495026 | doi = 10.1023/A:1020902915969 }}</ref> 
   |Symbol=MLN 
   |AltSymbols=
   |HGNCid=7141
   |Chromosome=6
   |Arm=p
   |Band=21
   |LocusSupplementaryData=.3-p21.2
   |ECnumber=
   |OMIM=158270
   |EntrezGene=4295
   |RefSeq=NM_001040109
   |UniProt=P12872
   |PDB=1lbj
}}

'''Motilin''' is a 22-amino acid [[Peptide hormone|polypeptide hormone]] in the motilin family that, in humans, is encoded by the ''MLN'' [[gene]].<ref name="pmid2574660">{{cite journal | vauthors = Daikh DI, Douglass JO, Adelman JP | title = Structure and expression of the human motilin gene | journal = Dna | volume = 8 | issue = 8 | pages = 615–21 | date = October 1989 | pmid = 2574660 | doi = 10.1089/dna.1989.8.615 }}</ref>

Motilin is secreted by [[Endocrine system|endocrine]] Mo cells<ref>{{Cite book |url= https://books.google.com/books?id=zZINAEddjA0C&pg=PA357&dq=mo+cell+motilin |title=Neuropeptide Function in the Gastrointestinal Tract| vauthors = Daniel EE |date=1990-12-11|publisher=CRC Press|isbn=9780849361586 }}</ref><ref>{{cite journal | vauthors = Goswami C, Shimada Y, Yoshimura M, Mondal A, Oda S, Tanaka T, Sakai T, Sakata I | title = Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus | journal = PLOS One | volume = 10 | issue = 6 | pages = e0131554 | date = 2015-06-26 | pmid = 26115342 | pmc = 4482737 | doi = 10.1371/journal.pone.0131554 }}</ref> (or M cells, these are not the same as the [[Microfold cell]]s (M cells) that are in [[Peyer's patch]]es) that are numerous in [[Intestinal gland|crypt]]s of the [[small intestine]], especially in the [[duodenum]] and [[jejunum]].<ref name="pmid18185063">{{cite journal | vauthors = Poitras P, Peeters TL | title = Motilin | journal = Current Opinion in Endocrinology, Diabetes and Obesity | volume = 15 | issue = 1 | pages = 54–7 | date = February 2008 | pmid = 18185063 | doi = 10.1097/MED.0b013e3282f370af }}</ref> It is released into the general circulation in humans at about 100-min intervals during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions; and it also stimulates endogenous release of the endocrine pancreas.<ref name="PUB00008516">{{cite journal | vauthors = Itoh Z | title = Motilin and clinical application | journal = Peptides | volume = 18 | issue = 4 | pages = 593–608 | year = 1997 | pmid = 9210180 | doi = 10.1016/S0196-9781(96)00333-6 }}</ref> Based on amino acid sequence, motilin is unrelated to other hormones. Because of its ability to stimulate gastric activity, it was named "motilin". Apart from in humans, the [[motilin receptor]] has been identified in the [[gastrointestinal tracts]] of [[pig]]s, [[rat]]s, [[cow]]s, and [[cat]]s, and in the central nervous system of [[rabbits]].

==Discovery==
Motilin was discovered by J.C. Brown when he introduced [[alkaline]] solution into duodena of dogs, which caused strong gastric contractions. Brown et al. predicted that [[alkali]] could either release stimulus to activate motor activity or prevent the secretion of inhibitory hormone. They isolated a [[polypeptide]] as a by-product from purification of [[secretin]] on carboxymethyl cellulose. They named this [[polypeptide]] "Motilin".<ref name="pmid4706833">{{cite journal | vauthors = Brown JC, Cook MA, Dryburgh JR | title = Motilin, a gastric motor activity stimulating polypeptide: the complete amino acid sequence | journal = Canadian Journal of Biochemistry | volume = 51 | issue = 5 | pages = 533–7 | date = May 1973 | pmid = 4706833 | doi = 10.1139/o73-066 }}</ref>

== Structure ==
Motilin has 22 [[amino acids]] and [[molecular weight]] of 2698 Daltons. In extract from human gut and plasma, there are two basic forms of motilin. The first molecular form is the [[polypeptide]] of 22 amino acids. The second form, on the other hand, is larger and contains the same 22 amino acids as the first form but includes an additional carboxyl-terminus end.<ref name="isbn0-7216-2888-5">{{cite book | vauthors = DeGroot LJ | veditors = McGuigan JE | title = Endocrinology | edition = | publisher = Saunders | location = Philadelphia | year = 1989 | origyear =  | quote = | isbn = 978-0-7216-2888-2 | oclc = | doi = | page = 2748 }}</ref>

The sequences of amino acids of motilin is: [[Phenylalanine|Phe]]-[[Valine|Val]]-[[Proline|Pro]]-[[Isoleucine|Ile]]-Phe-[[Threonine|Thr]]-[[Tyrosine|Tyr]]-[[Glycine|Gly]]-[[Glutamic acid|Glu]]-[[Leucine|Leu]]-[[Glutamine|Gln]]-[[Arginine|Arg]]-[[Methionine|Met]]-Gln-Glu-[[Lysine|Lys]]-Glu-Arg-[[Asparagine|Asn]]-Lys-Gly-Gln.<ref name="isbn0-7216-9398-9">{{cite book | vauthors = Williams RL | title = Textbook of endocrinology | edition = 6th | publisher = Saunders | location = Philadelphia | year = 1981 | origyear = | pages = 704–705 | quote = | isbn = 978-0-7216-9398-9 | oclc = | doi = }}</ref>

The structure and dynamics of the gastrointestinal peptide hormone motilin have been studied in the presence of isotropic q = 0.5 phospholipid [[model lipid bilayer|bicelles]]. The NMR solution structure of the peptide in acidic bicelle solution was determined from 203 NOE-derived distance constraints and six backbone [[torsion angle]] constraints. Dynamic properties for the <sup>13</sup>C<sub>α</sub>→<sup>1</sup>H vector in Leu-10 were determined for motilin specifically labeled with <sup>13</sup>C at this position by analysis of multiple-field relaxation data. The structure reveals an ordered [[alpha helix|alpha-helical]] conformation between Glu-9 and Lys-20. The N-terminus is also well structured with a turn resembling that of a classical [[turn (biochemistry)|beta-turn]]. The <sup>13</sup>C dynamics clearly show that motilin tumbles slowly in solution, with a correlation time characteristic of a large object.<ref name="pmid12495026"/>

==Stimulus==
Control of motilin secretion 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.<ref name="pmid717352">{{cite journal | vauthors = Itoh Z, Takeuchi S, Aizawa I, Mori K, Taminato T, Seino Y, Imura H, Yanaihara N | title = Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs | journal = The American Journal of Digestive Diseases | volume = 23 | issue = 10 | pages = 929–35 | date = October 1978 | pmid = 717352 | doi = 10.1007/BF01072469 }}</ref> [[Intravenous injection]] of glucose, which increases the release of insulin, is also found to inhibit cyclic elevation of plasma motilin.<ref name="pmid6388765">{{cite journal | vauthors = Lemoyne M, Wassef R, Tassé D, Trudel L, Poitras P | title = Motilin and the vagus in dogs | journal = Canadian Journal of Physiology and Pharmacology | volume = 62 | issue = 9 | pages = 1092–6 | date = September 1984 | pmid = 6388765 | doi = 10.1139/y84-182 }}</ref> Other studies on dogs have also suggested that motilin acted as endogenous ligand in positive feedback mechanism to stimulate the release of more motilin.<ref name="pmid6724277">{{cite journal | vauthors = Hall KE, Greenberg GR, El-Sharkawy TY, Diamant NE | title = Relationship between porcine motilin-induced migrating motor complex-like activity, vagal integrity, and endogenous motilin release in dogs | journal = Gastroenterology | volume = 87 | issue = 1 | pages = 76–85 | date = July 1984 | pmid = 6724277 | doi =  }}</ref>

== 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.<ref name="isbn0-7216-9398-9"/> 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]]<ref name="isbn0-07-022001-8">{{cite book | vauthors = Frohman LA, Felig P | veditors = Ghosh PK, O'Dorisio TM | title = Endocrinology & metabolism | edition = | publisher = McGraw-Hill, Medical Pub. Div | location = New York | year = 2001 | origyear =  | quote = | isbn = 978-0-07-022001-0 | oclc = | doi = | page = 1330 }}</ref>

==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.<ref name="pmid16185302">{{cite journal | vauthors = Galligan JJ, Vanner S | title = Basic and clinical pharmacology of new motility promoting agents | journal = Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society | volume = 17 | issue = 5 | pages = 643–53 | date = October 2005 | pmid = 16185302 | doi = 10.1111/j.1365-2982.2005.00675.x }}</ref> 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 receptor]]s, and agonists of these receptors, termed [[ghrelin]]s, can bring about similar effects to motilin agonists.

[[Camicinal]] is a Motilin agonist under development.

==Related peptides==
This domain is also found in [[ghrelin]], a growth hormone secretagogue synthesised by endocrine cells in the stomach. Ghrelin stimulates growth hormone secretagogue receptors in the pituitary. These receptors are distinct from the growth hormone-releasing hormone receptors, and, thus, provide a means of controlling pituitary growth hormone release by the gastrointestinal system.<ref name="PUB00007825">{{cite journal | vauthors = Kojima M, Hosoda H, Matsuo H, Kangawa K | title = Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor | journal = Trends in Endocrinology and Metabolism | volume = 12 | issue = 3 | pages = 118–22 | date = April 2001 | pmid = 11306336 | doi = 10.1016/S1043-2760(00)00362-3 }}</ref>
Erythromycin has an advantage over [[metoclopramide]] in gastric emptying due to lack of central nervous system side-effects. It is not approved by FDA to use for gastric emptying. For short duration for patients with diabetes and for those that must clear the stomach for any procedure, it may be used based on the physician's discretion with full understanding that it is not approved by FDA for this use.

==Human proteins ==
[[GHRL]];      Motilin;

== References ==
{{Reflist|2}}

== External links ==
* {{MeshName|Motilin}}
* {{GeorgiaPhysiology|6/6ch2/s6ch2_26}}

{{Neuropeptides}}
{{Gastrointestinal hormones}}
{{Signaling peptide/protein receptor modulators}}
{{InterPro content|IPR006737}}

[[Category:Intestinal hormones]]
[[Category:Motilin receptor agonists]]
[[Category:Protein domains]]
[[Category:Hormones]]