Top ▲

motilin receptor

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 297

Nomenclature: motilin receptor

Family: Motilin receptor

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 412 13q14.2 MLNR motilin receptor 9,23
Previous and Unofficial Names Click here for help
GPR38 | G protein-coupled receptor 38 | MOT-R | MTLR | MTLR1 [9]
Database Links Click here for help
Specialist databases
GPCRdb mtlr_human (Hs)
Other databases
Alphafold O43193 (Hs)
ChEMBL Target CHEMBL2203 (Hs)
Ensembl Gene ENSG00000102539 (Hs)
Entrez Gene 2862 (Hs)
Human Protein Atlas ENSG00000102539 (Hs)
KEGG Gene hsa:2862 (Hs)
OMIM 602885 (Hs)
Pharos O43193 (Hs)
RefSeq Nucleotide NM_001507 (Hs)
RefSeq Protein NP_001498 (Hs)
UniProtKB O43193 (Hs)
Wikipedia MLNR (Hs)
Natural/Endogenous Ligands Click here for help
motilin {Sp: Human, Pig}
Comments: aka GPR38

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]motilin (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 10.0 pKd 9
⤷ pKd 10.0 (Kd 1x10-10 M) [9]
motilin {Sp: Human, Pig} Peptide Ligand is endogenous in the given species Hs Full agonist 8.4 – 8.7 pKi 7,20-22
⤷ pKi 8.4 – 8.7 [7,20-22]
[Bpa1,Ile13]motilin (human) Peptide Hs Full agonist 7.9 pKi 7
⤷ pKi 7.9 [7]
[L-Bpa5,Ile13]motilin (human) Peptide Hs Full agonist 7.3 pKi 20
⤷ pKi 7.3 [20]
[D-Bpa5,Ile13]motilin (human) Peptide Hs Full agonist 6.4 pKi 20
⤷ pKi 6.4 [20]
DS-3801b free base Small molecule or natural product Hs Agonist 8.3 pEC50 37
⤷ pEC50 8.3 (EC50 5.3x10-9 M) [37]
camicinal Small molecule or natural product Primary target of this compound Hs Full agonist 7.9 pEC50 2,26
⤷ pEC50 7.9 [2,26]
mitemcinal Small molecule or natural product Oc Full agonist 7.5 – 7.8 pEC50 17,32
⤷ pEC50 7.5 – 7.8 [17,32]
azithromycin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Guide to Malaria Pharmacology Ligand Hs Full agonist 5.5 pEC50 4
⤷ pEC50 5.5 [4]
motilin {Sp: Rabbit} Peptide Hs Full agonist 9.7 pIC50 9
⤷ pIC50 9.7 [9]
[nLeu13,Glu14]motilin (human) Peptide Hs Full agonist 9.5 pIC50 9
⤷ pIC50 9.5 [9]
motilin-(1-13) (human) Peptide Hs Full agonist 9.5 pIC50 9
⤷ pIC50 9.5 [9]
motilin-(1-19) (human) Peptide Hs Full agonist 9.5 pIC50 9
⤷ pIC50 9.5 [9]
motilin {Sp: Dog} Peptide Hs Full agonist 9.3 pIC50 9
⤷ pIC50 9.3 [9]
[Leu13]motilin (human) Peptide Hs Full agonist 9.0 pIC50 9
⤷ pIC50 9.0 [9]
motilin-(1-12) (human) Peptide Hs Full agonist 9.0 pIC50 9
⤷ pIC50 9.0 [9]
[Phe3,Leu13]motilin (human) Peptide Hs Full agonist 8.9 pIC50 9
⤷ pIC50 8.9 [9]
mitemcinal Small molecule or natural product Oc Full agonist 8.1 – 8.2 pIC50 6
⤷ pIC50 8.1 – 8.2 [6]
motilin-(2-22) (human) Peptide Hs Full agonist 7.5 pIC50 9
⤷ pIC50 7.5 [9]
alemcinal Small molecule or natural product Hs Full agonist 7.2 pIC50 34
⤷ pIC50 7.2 [34]
KOS1326 Small molecule or natural product Hs Full agonist 7.2 pIC50 34
⤷ pIC50 7.2 [34]
motilin-(1-11) (human) Peptide Hs Full agonist 6.8 pIC50 9
⤷ pIC50 6.8 [9]
EM-523 Small molecule or natural product Hs Full agonist 6.6 pIC50 34
⤷ pIC50 6.6 [34]
ME67 Small molecule or natural product Hs Full agonist 6.5 pIC50 34
⤷ pIC50 6.5 [34]
ME4 Small molecule or natural product Hs Full agonist 6.3 pIC50 34
⤷ pIC50 6.3 [34]
roxithromycin Small molecule or natural product Approved drug Ligand has a PDB structure Hs Full agonist 6.2 pIC50 9
⤷ pIC50 6.2 [9]
erythromycin Small molecule or natural product Approved drug Ligand has a PDB structure Hs Full agonist 5.5 – 6.5 pIC50 9,34
⤷ pIC50 5.5 – 6.5 [9,34]
ME36 Small molecule or natural product 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 Value Parameter Reference
MA-2029 Small molecule or natural product Hs Antagonist 9.2 pA2 30
⤷ pA2 9.2 [30]
GM-109 Peptide Oc Antagonist 7.2 – 7.5 pA2 6,31
⤷ pA2 7.2 – 7.5 [6,31]
GM-109 Peptide Oc Antagonist 8.0 pIC50 12
⤷ pIC50 8.0 [12]
OHM-11526 Peptide 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 Click here for help
Transducer Effector/Response
Gq/G11 family
G12/G13 family 		Phospholipase C stimulation
References: 
Tissue Distribution Click here for help
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 Click here for help
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:  38
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 Click here for help
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:  38
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
Muscle contraction.
Species:  Human
Tissue:  Muscle strips from the stomach and upper small intestine.
References:  29
Vasoconstriction.
Species:  Human
Tissue:  Coronary artery.
References:  19
Biologically Significant Variants Click here for help
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 (6): 987-90. [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 (1): 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 (2): 146-51. [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 (38): 35518-22. [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 et al.. (1999) Receptor for motilin identified in the human gastrointestinal system. Science, 284 (5423): 2184-8. [PMID:10381885]

10. Feng X, Peeters TL, Tang M. (2007) Motilin activates neurons in the rat amygdala and increases gastric motility. Peptides, 28 (3): 625-31. [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 (1): 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 (3): 365-9. [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 (2): 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. Bioorg Med Chem Lett, 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 (6): 830-5. [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 (3): 1101-8. [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 (12): 9834-9. [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 (18): 12390-6. [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 (3): 426-34. [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 (1): G18-23. [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 (10): 1739-42. [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 (1): 95-9. [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 (11): 2446-9. [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 (6): 1485-91. [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 (3): 223-30. [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 (3): 1397-405. [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 (1-2): 119-28. [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 (4): 1223-7. [PMID:12054506]

37. Toda N, Shida T, Takano R, Katagiri T, Hirouchi M, Abe M, Soma K, Nakagami Y, Yamazaki M. (2022) Discovery of DS-3801b, a non-macrolide GPR38 agonist with N-methylanilide structure. Bioorg Med Chem Lett, 59: 128554. [PMID:35051575]

38. 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 (1): 27-35. [PMID:11169123]

Contributors

Show »

How to cite this page