motilin receptor | Motilin receptor | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

motilin receptor

Target id: 297

Nomenclature: motilin receptor

Family: Motilin receptor

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for motilin receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 412 13q14-q21 MLNR motilin receptor 9,23
Previous and Unofficial Names
MOT-R | MTLR | GPR38 [23] | MTLR1 [9] | G protein-coupled receptor 38
Database Links
Specialist databases
GPCRDB mtlr_human (Hs)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
motilin {Sp: Human, Pig}
Comments: aka GPR38

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]motilin (human) Hs Full agonist 10.0 pKd 9
pKd 10.0 (Kd 1x10-10 M) [9]
motilin {Sp: Human, Pig} Hs Full agonist 8.4 – 8.7 pKi 7,20-22
pKi 8.4 – 8.7 [7,20-22]
[Bpa1,Ile13]motilin (human) Hs Full agonist 7.9 pKi 7
pKi 7.9 [7]
[L-Bpa5,Ile13]motilin (human) Hs Full agonist 7.3 pKi 20
pKi 7.3 [20]
[D-Bpa5,Ile13]motilin (human) Hs Full agonist 6.4 pKi 20
pKi 6.4 [20]
camicinal Hs Full agonist 7.9 pEC50 2,26
pEC50 7.9 [2,26]
mitemcinal Oc Full agonist 7.5 – 7.8 pEC50 17,32
pEC50 7.5 – 7.8 [17,32]
azithromycin Hs Full agonist 5.5 pEC50 4
pEC50 5.5 [4]
motilin {Sp: Rabbit} Hs Full agonist 9.7 pIC50 9
pIC50 9.7 [9]
[nLeu13,Glu14]motilin (human) Hs Full agonist 9.5 pIC50 9
pIC50 9.5 [9]
motilin-(1-13) (human) Hs Full agonist 9.5 pIC50 9
pIC50 9.5 [9]
motilin-(1-19) (human) Hs Full agonist 9.5 pIC50 9
pIC50 9.5 [9]
motilin {Sp: Dog} Hs Full agonist 9.3 pIC50 9
pIC50 9.3 [9]
[Leu13]motilin (human) Hs Full agonist 9.0 pIC50 9
pIC50 9.0 [9]
motilin-(1-12) (human) Hs Full agonist 9.0 pIC50 9
pIC50 9.0 [9]
[Phe3,Leu13]motilin (human) Hs Full agonist 8.9 pIC50 9
pIC50 8.9 [9]
mitemcinal Oc Full agonist 8.1 – 8.2 pIC50 6
pIC50 8.1 – 8.2 [6]
motilin-(2-22) (human) Hs Full agonist 7.5 pIC50 9
pIC50 7.5 [9]
alemcinal Hs Full agonist 7.2 pIC50 34
pIC50 7.2 [34]
KOS1326 Hs Full agonist 7.2 pIC50 34
pIC50 7.2 [34]
motilin-(1-11) (human) Hs Full agonist 6.8 pIC50 9
pIC50 6.8 [9]
EM-523 Hs Full agonist 6.6 pIC50 34
pIC50 6.6 [34]
ME67 Hs Full agonist 6.5 pIC50 34
pIC50 6.5 [34]
ME4 Hs Full agonist 6.3 pIC50 34
pIC50 6.3 [34]
roxithromycin Hs Full agonist 6.2 pIC50 9
pIC50 6.2 [9]
erythromycin-A Hs Full agonist 5.5 – 6.5 pIC50 9,34
pIC50 5.5 – 6.5 [9,34]
ME36 Hs Full agonist 4.7 pIC50 34
pIC50 4.7 [34]
View species-specific agonist tables
Agonist Comments
The lower affinity of [D-Bpa5,Ile13]motilin over [L-Bpa5,Ile13]motilin [20] suggests that the fifth amino acid residue of motilin is involved in stabilising the bioactive conformation. Mitemcinal has been shown to be an agonist at the motilin receptor in other mammalian species [17,32].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
MA-2029 Hs Antagonist 9.2 pA2 30
pA2 9.2 [30]
GM-109 Oc Antagonist 7.2 – 7.5 pA2 6,31
pA2 7.2 – 7.5 [6,31]
GM-109 Oc Antagonist 8.0 pIC50 12
pIC50 8.0 [12]
OHM-11526 Hs Antagonist - - 8
[8]
View species-specific antagonist tables
Antagonist Comments
The antagonists reported have been tested on the porcine and rabbit Motilin receptors.
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family
G12/G13 family
Phospholipase C stimulation
References: 
Tissue Distribution
Gastrointestinal tract: esophagus, stomach, duodenum, jejunum, ileum, proximal colon, distal colon (mucosal and muscle layers).
Species:  Human
Technique:  RT-PCR.
References:  33
Stomach, thyroid, bone marrow.
Species:  Human
Technique:  RNase protection assay.
References:  23
Gastrointestinal tract: small intestine, stomach, colon (muscle layers and myenteric plexus).
Species:  Human
Technique:  Immunohistochemistry.
References:  33
Gastric antrum and duodenum.
Species:  Human
Technique:  Radioligand binding.
References:  24
Functional Assays
Measurement of Ca2+ levels in CHO cells transfected with the human motilin receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Increase in Ca2+ concentration.
References:  7,20,34,36
Measurement of Ca2+ levels in HEK 293 cells transfected with the human motilin receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in Ca2+ concentration.
References:  5,9
Measurement of Ca2+ levels in cultured human colonic smooth-muscle cells endogenously expressing the motilin receptor.
Species:  Human
Tissue:  Primary cultures of colonic smooth-muscle cells.
Response measured:  Increase in Ca2+ concentration.
References:  37
Measurement of Ca2+ levels in TE671 cells (a cell line originating from the human cerebellum), endogenously expressing the motilin receptor.
Species:  Human
Tissue:  TE671 cells.
Response measured:  Increase in Ca2+ concentration.
References:  35
Measurement of Ca2+ levels in COS-1 cells transfected with the human motilin receptor.
Species:  Human
Tissue:  COS-1 cells.
Response measured:  Increase in Ca2+ concentration.
References:  21-22
Physiological Functions
Muscle contraction.
Species:  Human
Tissue:  Muscle strips from the stomach and upper small intestine.
References:  29
Vasoconstriction.
Species:  Human
Tissue:  Coronary artery.
References:  19
Stimulation of gastric motility (following intracerebroventricular microinjection of erythromycin).
Species:  Rat
Tissue:  In vivo (stomach).
References:  15
Stimulation of colonic transit.
Species:  Human
Tissue:  In vivo (colon).
References:  28
Stimulation of gall bladder emptying and increase in antral contraction frequency.
Species:  Human
Tissue:  In vivo (gall bladder).
References:  18
Stimulation of food intake.
Species:  Mouse
Tissue:  In vivo.
References:  1
Decrease in anxiety.
Species:  Mouse
Tissue:  In vivo.
References:  25
Muscle contraction.
Species:  Human
Tissue:  Circular smooth muscle strips of the colon.
References:  37
Regulation of migrating motor complexes.
Species:  Human
Tissue:  In vivo.
References:  13-14
Stimulation of gastric motility.
Species:  Human
Tissue:  In vivo (stomach).
References:  3,16
Stimulation of gastric motility (following microinjection of motilin into the hippocampus).
Species:  Rat
Tissue:  In vivo (stomach).
References:  11
Stimulation of gall bladder emptying.
Species:  Human
Tissue:  In vivo (gall bladder).
References:  27
Stimulation of gastric motility (following microinjection of motilin into the basomedial amygdala nucleus).
Species:  Rat
Tissue:  In vivo (stomach).
References:  10
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  A splice variant of the motilin receptor is known to exist, containing 386 amino acids and only 5 transmembrane domains.
Amino acids:  386
References:  9

References

Show »

1. Asakawa A, Inui A, Momose K, Ueno N, Fujino MA, Kasuga M. (1998) Motilin increases food intake in mice. Peptides, 19: 987-990. [PMID:9700745]

2. Barshop K, Kuo B. (2015) The investigational drug camicinal for the treatment of gastroparesis. Expert Opin Investig Drugs, 24 (1): 133-140. [PMID:25341626]

3. Boivin MA, Carey MC, Levy H. (2003) Erythromycin accelerates gastric emptying in a dose-response manner in healthy subjects. Pharmacotherapy, 23: 5-8. [PMID:12523456]

4. Broad J, Sanger GJ. (2013) The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin. Br. J. Pharmacol., 168 (8): 1859-67. [PMID:23190027]

5. Carreras CW, Siani MA, Santi DV, Dillon SB. (2002) Stable expression of a synthetic gene for the human motilin receptor: use in an aequorin-based receptor activation assay. Anal Biochem, 300: 146-151. [PMID:11779105]

6. Clark MJ, Wright T, Bertrand PP, Bornstein JC, Jenkinson KM, Verlinden M, Furness JB. (1999) Erythromycin derivatives ABT 229 and GM 611 act on motilin receptors in the rabbit duodenum. Clin. Exp. Pharmacol. Physiol., 26 (3): 242-5. [PMID:10081621]

7. Coulie B, Matsuura B, Dong M, Hadac EM, Pinon DI, Feighner SD, Howard AD, Miller LJ. (2001) Identification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling. J Biol Chem, 276: 35518-35522. [PMID:11461914]

8. Farrugia G, Macielag MJ, Peeters TL, Sarr MG, Galdes A, Szurszewski JH. (1997) Motilin and OHM-11526 activate a calcium current in human and canine jejunal circular smooth muscle. Am. J. Physiol., 273 (2 Pt 1): G404-12. [PMID:9277420]

9. 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. (1999) Receptor for motilin identified in the human gastrointestinal system. Science, 284: 2184-2188. [PMID:10381885]

10. Feng X, Peeters TL, Tang M. (2007) Motilin activates neurons in the rat amygdala and increases gastric motility. Peptides, 28: 625-631. [PMID:17222944]

11. Guan Y, Tang M, Jiang Z, Peeters TL. (2003) Excitatory effects of motilin in the hippocampus on gastric motility in rats. Brain Res, 984: 33-41. [PMID:12932837]

12. Haramura M, Okamachi A, Tsuzuki K, Yogo K, Ikuta M, Kozono T, Takanashi H, Murayama E. (2002) Design and synthesis of motilin antagonists derived from the [1-4] fragment of porcine motilin. J. Med. Chem., 45 (3): 670-5. [PMID:11806718]

13. Jadcherla SR, Berseth CL. (2002) Effect of erythromycin on gastroduodenal contractile activity in developing neonates. J Pediatr Gastroenterol Nutr, 34: 16-22. [PMID:11753158]

14. Jadcherla SR, Klee G, Berseth CL. (1997) Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants. Pediatr Res, 42: 365-369. [PMID:9284278]

15. Jia YD, Liu CQ, Tang M, Jiang ZY. (2007) Expression of motilin in the hypothalamus and the effect of central erythromycin on gastric motility in diabetic rats. Neurosci Bull, 23: 75-82. [PMID:17592529]

16. Kamerling IM, van Haarst AD, Burggraaf J, Schoemaker RC, de Kam ML, Heinzerling H, Cohen AF, Masclee AA. (2004) Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function. Br J Clin Pharmacol, 57: 393-401. [PMID:15025736]

17. Koga H, Sato T, Tsuzuki K, Onoda H, Kuboniwa H, Takanashi H. (1994) Potent, acid-stable and orally active macrolide-type motilin receptor agonists, GM-611 and the derivatives. Bioorganic and Medicinal Chemistry Letters, 4 (11): 1347-1352.

18. Luiking YC, Peeters TL, Stolk MF, Nieuwenhuijs VB, Portincasa P, Depoortere I, van Berge Henegouwen GP, Akkermans LM. (1998) Motilin induces gall bladder emptying and antral contractions in the fasted state in humans. Gut, 42: 830-835. [PMID:9691922]

19. Maguire JJ, Kuc RE, Davenport AP. (2004) Motilin mediates vasoconstriction in human coronary artery in vitro. Proceedings of the British Pharmacological Society, pA2 online.,: -.

20. Matsuura B, Dong M, Coulie B, Pinon DI, Miller LJ. (2005) Demonstration of a specific site of covalent labeling of the human motilin receptor using a biologically active photolabile motilin analog. J Pharmacol Exp Ther, 313: 1101-1108. [PMID:15677347]

21. Matsuura B, Dong M, Miller LJ. (2002) Differential determinants for peptide and non-peptidyl ligand binding to the motilin receptor. Critical role of second extracellular loop for peptide binding and action. J Biol Chem, 277: 9834-9839. [PMID:11781320]

22. Matsuura B, Dong M, Naik S, Miller LJ, Onji M. (2006) Differential contributions of motilin receptor extracellular domains for peptide and non-peptidyl agonist binding and activity. J Biol Chem, 281: 12390-12396. [PMID:16531413]

23. McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL, Smith RG, Howard AD, Van der Ploeg LH. (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: 426-434. [PMID:9441746]

24. Miller P, Roy A, St-Pierre S, Dagenais M, Lapointe R, Poitras P. (2000) Motilin receptors in the human antrum. Am J Physiol Gastrointest Liver Physiol, 278: G18-G23. [PMID:10644557]

25. Momose K, Inui A, Asakawa A, Ueno N, Nakajima M, Kasuga M. (1998) Anxiolytic effect of motilin and reversal with GM-109, a motilin antagonist, in mice. Peptides, 19: 1739-1742. [PMID:9880080]

26. Sanger GJ, Westaway SM, Barnes AA, Macpherson DT, Muir AI, Jarvie EM, Bolton VN, Cellek S, Näslund E, Hellström PM et al.. (2009) GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol. Motil., 21 (6): 657-64, e30-1. [PMID:19374732]

27. Sengupta S, Modak P, McCauley N, O'Donnell LJ. (2006) Effect of oral clarithromycin on gall-bladder motility in normal subjects and those with gall-stones. Aliment Pharmacol Ther, 24: 95-99. [PMID:16803607]

28. Sharma SS, Bhargava N, Mathur SC. (1995) Effect of oral erythromycin on colonic transit in patients with idiopathic constipation. A pilot study. Dig Dis Sci, 40: 2446-2449. [PMID:7587829]

29. Strunz U, Domschke W, Mitznegg P, Domschke S, Schubert E, Wünsch E, Jaeger E, Demling L. (1975) Analysis of the motor effects of 13-norleucine motilin on the rabbit, guinea pig, rat, and human alimentary tract in vitro. Gastroenterology, 68: 1485-1491. [PMID:1132629]

30. Sudo H, Yoshida S, Ozaki K, Muramatsu H, Onoma M, Yogo K, Kamei K, Cynshi O, Kuromaru O, Peeters TL et al.. (2008) Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits. Eur. J. Pharmacol., 581 (3): 296-305. [PMID:18164286]

31. Takanashi H, Yogo K, Ozaki K, Ikuta M, Akima M, Koga H, Nabata H. (1995) GM-109: a novel, selective motilin receptor antagonist in the smooth muscle of the rabbit small intestine. J. Pharmacol. Exp. Ther., 273 (2): 624-8. [PMID:7752063]

32. Takanashi H, Yogo K, Ozaki K, Koga H, Itoh Z, Omura S. (2007) In vitro pharmacological characterization of mitemcinal (GM-611), the first acid-resistant non-peptide motilin receptor agonist, in smooth muscle of rabbit small intestine. Pharmacology, 79 (3): 137-48. [PMID:17183187]

33. Takeshita E, Matsuura B, Dong M, Miller LJ, Matsui H, Onji M. (2006) Molecular characterization and distribution of motilin family receptors in the human gastrointestinal tract. J Gastroenterol, 41: 223-230. [PMID:16699856]

34. Thielemans L, Depoortere I, Perret J, Robberecht P, Liu Y, Thijs T, Carreras C, Burgeon E, Peeters TL. (2005) Desensitization of the human motilin receptor by motilides. J Pharmacol Exp Ther, 313: 1397-1405. [PMID:15764739]

35. Thielemans L, Depoortere I, Van Assche G, Bender E, Peeters TL. (2001) Demonstration of a functional motilin receptor in TE671 cells from human cerebellum. Brain Res, 895: 119-128. [PMID:11259768]

36. Thielemans L, Depoortere I, Vanden Broeck J, Peeters TL. (2002) The motilin pharmacophore in CHO cells expressing the human motilin receptor. Biochem Biophys Res Commun, 293: 1223-1227. [PMID:12054506]

37. Van Assche G, Depoortere I, Thijs T, Missiaen L, Penninckx F, Takanashi H, Geboes K, Janssens J, Peeters TL. (2001) Contractile effects and intracellular Ca2+ signalling induced by motilin and erythromycin in the circular smooth muscle of human colon. Neurogastroenterol Motil, 13: 27-35. [PMID:11169123]

Contributors

Show »

How to cite this page

Anthony P. Davenport.
Motilin receptor: motilin receptor. Last modified on 15/03/2017. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=297.