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Gene Review

MLNR  -  motilin receptor

Homo sapiens

Synonyms: G-protein coupled receptor 38, GPR38, MTLR, MTLR1, Motilin receptor
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Disease relevance of MLNR


Psychiatry related information on MLNR


High impact information on MLNR

  • The macrolide antibiotic erythromycin also interacted with the cloned motilin receptor, providing a molecular basis for its effects on the human GI tract [7].
  • The motilin receptor is expressed in enteric neurons of the human duodenum and colon [7].
  • The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied [8].
  • These results support the presence of functionally important disulfide bonds in the motilin receptor ectodomain and demonstrate that the structural determinants for binding and biological activity of peptide and non-peptidyl agonist ligands are distinct, with a broad extracellular perimembranous base contributing to normal motilin binding [9].
  • Here, we have extended that work, examining the other predicted extracellular domains of the motilin receptor by using sequential deletions of segments ranging from one to six amino acid residues and site-directed alanine replacement mutagenesis approaches [9].

Biological context of MLNR


Anatomical context of MLNR


Associations of MLNR with chemical compounds

  • The potencies to induce Ca(2+) fluxes correlated strongly with rabbit binding and contractility data, suggesting that the cloned receptor is indeed the motilin receptor, responsible for contractile effects [15].
  • There is a concomitant decrease in the size of the alpha/beta ratio which is greater for ADRR cells than for MLNR cells [16].
  • In contrast both the drug-resistant sublines (MCF-7 ADRR and the melphalan-resistant line MCF-7 MLNR) are radiosensitized by GSH depletion under both aerated and hypoxic conditions [17].
  • Two sublines, one resistant to adriamycin (ADRR) and the other to melphalan (MLNR), have been selected by exposure to stepwise increasing concentrations of the respective drugs [16].
  • A Schild plot revealed that EM-523 was a competitive inhibitor of motilin receptor binding in man and in rabbit [18].

Regulatory relationships of MLNR


Other interactions of MLNR


Analytical, diagnostic and therapeutic context of MLNR


  1. Motilin and motilin receptors: characterization and functional significance. Depoortere, I. Verh. K. Acad. Geneeskd. Belg. (2001) [Pubmed]
  2. Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial. Talley, N.J., Verlinden, M., Geenen, D.J., Hogan, R.B., Riff, D., McCallum, R.W., Mack, R.J. Gut (2001) [Pubmed]
  3. Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial. Talley, N.J., Verlinden, M., Snape, W., Beker, J.A., Ducrotte, P., Dettmer, A., Brinkhoff, H., Eaker, E., Ohning, G., Miner, P.B., Mathias, J.R., Fumagalli, I., Staessen, D., Mack, R.J. Aliment. Pharmacol. Ther. (2000) [Pubmed]
  4. Efficacy of a motilin receptor agonist (ABT-229) for the treatment of gastro-oesophageal reflux disease. Chen, C.L., Orr, W.C., Verlinden, M.H., Dettmer, A., Brinkhoff, H., Riff, D., Schwartz, S., Soloway, R.D., Krause, R., Lanza, F., Mack, R.J. Aliment. Pharmacol. Ther. (2002) [Pubmed]
  5. Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy. Catnach, S.M., Ballinger, A.B., Stevens, M., Fairclough, P.D., Trembath, R.C., Drury, P.L., Watkins, P.J. Gut (1993) [Pubmed]
  6. Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants. Jadcherla, S.R., Klee, G., Berseth, C.L. Pediatr. Res. (1997) [Pubmed]
  7. Receptor for motilin identified in the human gastrointestinal system. Feighner, S.D., Tan, C.P., McKee, K.K., Palyha, O.C., Hreniuk, D.L., Pong, S.S., Austin, C.P., Figueroa, D., MacNeil, D., Cascieri, M.A., Nargund, R., Bakshi, R., Abramovitz, M., Stocco, R., Kargman, S., O'Neill, G., Van Der Ploeg, L.H., Evans, J., Patchett, A.A., Smith, R.G., Howard, A.D. Science (1999) [Pubmed]
  8. Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones. Catnach, S.M., Fairclough, P.D., Trembath, R.C., O'Donnell, L.J., McLean, A.M., Law, P.A., Wickham, J.E. Gastroenterology (1992) [Pubmed]
  9. Differential Contributions of Motilin Receptor Extracellular Domains for Peptide and Non-peptidyl Agonist Binding and Activity. Matsuura, B., Dong, M., Naik, S., Miller, L.J., Onji, M. J. Biol. Chem. (2006) [Pubmed]
  10. Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. McKee, K.K., Tan, C.P., Palyha, O.C., Liu, J., Feighner, S.D., Hreniuk, D.L., Smith, R.G., Howard, A.D., Van der Ploeg, L.H. Genomics (1997) [Pubmed]
  11. Growth hormone secretagogue receptor family members and ligands. Smith, R.G., Leonard, R., Bailey, A.R., Palyha, O., Feighner, S., Tan, C., Mckee, K.K., Pong, S.S., Griffin, P., Howard, A. Endocrine (2001) [Pubmed]
  12. Characterization of agonist-induced motilin receptor trafficking and its implications for tachyphylaxis. Lamian, V., Rich, A., Ma, Z., Li, J., Seethala, R., Gordon, D., Dubaquie, Y. Mol. Pharmacol. (2006) [Pubmed]
  13. Motilin receptors in the human antrum. Miller, P., Roy, A., St-Pierre, S., Dagenais, M., Lapointe, R., Poitras, P. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  14. Molecular characterization and distribution of motilin family receptors in the human gastrointestinal tract. Takeshita, E., Matsuura, B., Dong, M., Miller, L.J., Matsui, H., Onji, M. J. Gastroenterol. (2006) [Pubmed]
  15. The motilin pharmacophore in CHO cells expressing the human motilin receptor. Thielemans, L., Depoortere, I., Vanden Broeck, J., Peeters, T.L. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Radiation response of drug-resistant variants of a human breast cancer cell line. Lehnert, S., Greene, D., Batist, G. Radiat. Res. (1989) [Pubmed]
  17. Radiation response of drug-resistant variants of a human breast cancer cell line: the effect of glutathione depletion. Lehnert, S., Greene, D., Batist, G. Radiat. Res. (1990) [Pubmed]
  18. The erythromycin derivative EM-523 is a potent motilin agonist in man and in rabbit. Depoortere, I., Peeters, T.L., Vantrappen, G. Peptides (1990) [Pubmed]
  19. Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum. Depoortere, I., Thijs, T., Thielemans, L., Robberecht, P., Peeters, T.L. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  20. Identification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling. Coulie, B., Matsuura, B., Dong, M., Hadac, E.M., Pinon, D.I., Feighner, S.D., Howard, A.D., Miller, L.J. J. Biol. Chem. (2001) [Pubmed]
  21. Growth hormone releasing substances: types and their receptors. Smith, R.G., Palyha, O.C., Feighner, S.D., Tan, C.P., McKee, K.K., Hreniuk, D.L., Yang, L., Morriello, G., Nargund, R., Patchett, A.A., Howard, A.D. Horm. Res. (1999) [Pubmed]
  22. Demonstration of a functional motilin receptor in TE671 cells from human cerebellum. Thielemans, L., Depoortere, I., Van Assche, G., Bender, E., Peeters, T.L. Brain Res. (2001) [Pubmed]
  23. Delineation of the motilin domain involved in desensitization and internalization of the motilin receptor by using full and partial antagonists. Mitselos, A., Depoortere, I., Peeters, T.L. Biochem. Pharmacol. (2007) [Pubmed]
  24. EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum. Satoh, M., Sakai, T., Sano, I., Fujikura, K., Koyama, H., Ohshima, K., Itoh, Z., Omura, S. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
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