Abstract
Background
Motilin and ghrelin have been recognized as important endogenous regulators of gastrointestinal motor function in mammals, mediated respectively by the motilin receptor and by the closely related ghrelin receptor. The aims of this study were to explore the distribution of motilin and ghrelin receptors along the human gastrointestinal tract and to establish the molecular nature of the human motilin receptor.
Methods
Post mortem and surgical human tissue specimens with no hemorrhage, necrosis, or tumor were obtained from various parts of the gastrointestinal tract. We analyzed levels of expression of mRNA for motilin and ghrelin receptors and examined their molecular identities. Portions of some specimens were also studied by immunohistochemistry for expression of the motilin and ghrelin receptor.
Results
The long form of the motilin receptor, but not the short form, was expressed in all parts of the gastrointestinal tract, and expressed at higher levels in muscle than in mucosa. Motilin receptor immunoreactivity was present in muscle cells and the myenteric plexus, but not in mucosal or submucosal cells. In contrast, ghrelin receptor mRNA was expressed equally in all parts of the gastrointestinal tract, with similar levels of expression in mucosal and muscle layers.
Conclusions
Both the motilin and ghrelin receptors are expressed along the human gastrointestinal tract, but they have clearly distinct distributions in regard to both level and layer. The diffuse muscle expression of the motilin receptor, at both the levels of the gene and the protein product, along the entire gastrointestinal tract makes it a useful potential target for motilide drugs for dysmotility.
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References
Z Itoh I Aizawa T Sekiguchi (1982) ArticleTitleThe digestive migrating complex and its significance in man Clin Gastroenterol 11 497–521 Occurrence Handle1:STN:280:DyaL3s%2FltFKjtg%3D%3D Occurrence Handle6754170
Y Kondo K Torii Z Itoh S Omura (1998) ArticleTitleErythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of 125I-motilin to duodenal muscle Biochem Biophys Res Commun 150 877–82 Occurrence Handle10.1016/0006-291X(88)90474-3
T Peeters G Matthijs I Depoortere T Cachet J Hoogmartens G Vantrappen (1989) ArticleTitleErythromycin is a motilin receptor agonist Am J Physiol 257 G470–4 Occurrence Handle1:CAS:528:DyaL1MXlvVKqtbo%3D Occurrence Handle2782416
P Poitras D Gagnon S St Pierre (1992) ArticleTitleN-terminal portion of motilin determines its biological activity Biochem Biophys Res Commun 183 36–40 Occurrence Handle10.1016/0006-291X(92)91605-P Occurrence Handle1:CAS:528:DyaK38Xhs1Knt7s%3D Occurrence Handle1543506
M Satoh T Sakai H Koyama Y Shiba Z Itoh (1995) ArticleTitleImmunocytochemical localization of motilin-containing cells in the rabbit gastrointestinal tract Peptides 16 883–7 Occurrence Handle10.1016/0196-9781(95)00046-M Occurrence Handle1:CAS:528:DyaK2MXntFSgurc%3D Occurrence Handle7479330
V Bormans T Peeters G Vantrappen (1986) ArticleTitleMotilin receptors in rabbit stomach and small intestine Regul Pept 15 143–53 Occurrence Handle10.1016/0167-0115(86)90084-4 Occurrence Handle1:CAS:528:DyaL28Xls1Gmtr4%3D Occurrence Handle3786836
T Peeters V Bormans G Vantrappen (1988) ArticleTitleComparison of motilin binding to crude homogenates of human and canine gastrointestinal smooth muscle tissue Regul Pept 23 171–82 Occurrence Handle10.1016/0167-0115(88)90025-0 Occurrence Handle1:CAS:528:DyaL1MXovFSmsw%3D%3D Occurrence Handle3231745
P Miller L Trudel S St Pierre H Takanashi P Poitras (2000) ArticleTitleNeural and muscular receptors for motilin in the rabbit colon Peptides 21 283–7 Occurrence Handle10.1016/S0196-9781(99)00198-9 Occurrence Handle1:CAS:528:DC%2BD3cXitlOrurw%3D Occurrence Handle10764957
SD Feighner CP Tan KK McKee OC Palyha DL Hreniul SS Pong et al. (1999) ArticleTitleReceptor for motilin identified in the human gastrointestinal system Science 284 2184–8 Occurrence Handle10.1126/science.284.5423.2184 Occurrence Handle1:CAS:528:DyaK1MXkt1Kmsr0%3D Occurrence Handle10381885
KK McKee CP Tan OC Palyha J Liu SD Feighner DL Hreniuk et al. (1997) ArticleTitleCloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors Genomics 46 426–34 Occurrence Handle10.1006/geno.1997.5069 Occurrence Handle1:CAS:528:DyaK1cXmt12gsA%3D%3D Occurrence Handle9441746
B Coulie B Matsuura M Dong EM Hadac DI Pinon SD Feighner et al. (2001) ArticleTitleIdentification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling J Biol Chem 276 35518–22 Occurrence Handle10.1074/jbc.M104489200 Occurrence Handle1:CAS:528:DC%2BD3MXntFahs78%3D Occurrence Handle11461914
B Matsuura M Dong LJ Miller (2002) ArticleTitleDifferential determinants for peptide and non-peptidyl ligand binding to the motilin receptor J Biol Chem 277 9834–9 Occurrence Handle10.1074/jbc.M111051200 Occurrence Handle1:CAS:528:DC%2BD38XisVylsL0%3D Occurrence Handle11781320
B Matsuura M Dong B Coulie DI Pinon LJ Miller (2005) ArticleTitleDemonstration of a specific site of covalent labeling of the human motilin receptor using a biologically active photolabile motilin analogue J Pharmacol Exp Ther 313 1101–8 Occurrence Handle10.1124/jpet.104.081562 Occurrence Handle1:CAS:528:DC%2BD2MXkslekt7Y%3D Occurrence Handle15677347
M Kojima H Hosoda Y Date M Nakazato H Matsuo K Kangawa (1999) ArticleTitleGhrelin is a growth hormone-releasing acylated peptide from stomach Nature 402 656–60 Occurrence Handle10.1038/45230 Occurrence Handle1:CAS:528:DC%2BD3cXjs1Ki Occurrence Handle10604470
M Nakazato N Murakami Y Date M Kojima H Matsuo K Kangawa et al. (2001) ArticleTitleA role for ghrelin in the central regulation of feeding Nature 409 194–8 Occurrence Handle10.1038/35051587 Occurrence Handle1:CAS:528:DC%2BD3MXlvFSmsg%3D%3D Occurrence Handle11196643
Y Masuda T Tanaka N Inomata N Ohmura S Tanaka Z Itoh et al. (2000) ArticleTitleGhrelin stimulates gastric acid secretion and motility in rats Biochem Biophys Res Commun 276 905–8 Occurrence Handle10.1006/bbrc.2000.3568 Occurrence Handle1:CAS:528:DC%2BD3cXntFOqsrg%3D Occurrence Handle11027567
NB Dass M Munonyara AK Bassil GJ Hervieu S Osbourne S Corcoran et al. (2003) ArticleTitleGrowth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin Neuroscience 120 443–53 Occurrence Handle10.1016/S0306-4522(03)00327-0 Occurrence Handle1:CAS:528:DC%2BD3sXlvVCltrk%3D Occurrence Handle12890514
L Thielemans I Depoortere GV Assche E Bender TL Peeters (2001) ArticleTitleDemonstration of a functional motilin receptor in TE671 cells from human cerebellum Brain Res 895 119–28 Occurrence Handle10.1016/S0006-8993(01)02055-8 Occurrence Handle1:CAS:528:DC%2BD3MXitVOnsrY%3D Occurrence Handle11259768
MH Holtmann S Ganguli EM Hadac V Dolu LJ Miller (1996) ArticleTitleMultiple extracellular loop domains contribute critical determinants for agonist binding and activation of the secretin receptor J Biol Chem 271 14944–9 Occurrence Handle10.1074/jbc.271.25.14944 Occurrence Handle1:CAS:528:DyaK28XjvVWmtL8%3D Occurrence Handle8663161
A Inui (2001) ArticleTitleGhrelin: an orexigenic and somatotrophic signal from the stomach Nat Rev Neurosci 2 551–60 Occurrence Handle10.1038/35086018 Occurrence Handle1:CAS:528:DC%2BD3MXmtVaqtbo%3D Occurrence Handle11483998
G Muccioli M Tschop M Papotti R Deghenghi M Heiman E Ghigo (2002) ArticleTitleNeuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity Eur J Pharmacol 440 235–54 Occurrence Handle10.1016/S0014-2999(02)01432-2 Occurrence Handle1:CAS:528:DC%2BD38XjsVSktbw%3D Occurrence Handle12007539
A Asakawa A Inui K Momose N Ueno M Fujino M Kasuga (1998) ArticleTitleMotilin increases food intake in mice Peptides 19 987–90 Occurrence Handle10.1016/S0196-9781(97)00477-4 Occurrence Handle1:CAS:528:DyaK1cXltFGqtbY%3D Occurrence Handle9700745
I Depoortere TL Peeters (1997) ArticleTitleDemonstration and characterization of motilin-binding sites in the rabbit cerebellum Am J Physiol 272 G994–9 Occurrence Handle1:CAS:528:DyaK2sXjsFChu74%3D Occurrence Handle9176206
K Momose A Inui A Asakawa N Ueno M Nakajima M Kasuga (1998) ArticleTitleAnxiolytic effect of motilin and reversal with GM-109, a motilin antagonist, in mice Peptides 19 1739–42 Occurrence Handle10.1016/S0196-9781(98)00131-4 Occurrence Handle1:CAS:528:DyaK1MXisFWntQ%3D%3D Occurrence Handle9880080
A Asakawa A Inui T Kaga H Yuzuriha T Nagata N Ueno et al. (2001) ArticleTitleGhrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin Gastroenterology 120 337–45 Occurrence Handle10.1053/gast.2001.22158 Occurrence Handle1:CAS:528:DC%2BD3MXhtlKlt7Y%3D Occurrence Handle11159873
A Inui A Asakawa CY Bowers G Mantovani A Laviano MM Meguid et al. (2004) ArticleTitleGhrelin, appetite and gastric motility: the emerging role of the stomach as an endocrine organ FASEB J 19 439–56 Occurrence Handle10.1096/fj.03-0641rev Occurrence Handle1:CAS:528:DC%2BD2cXisFSrs7Y%3D
K Fujino A Inui A Asakawa N Kihara M Fujimura M Fujimiya (2003) ArticleTitleGhrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats J Physiol 550 227–40 Occurrence Handle10.1113/jphysiol.2003.040600 Occurrence Handle1:CAS:528:DC%2BD3sXmtlyisrc%3D Occurrence Handle12837928
JET Fox EE Daniel J Jury AE Fox SM Collins (1983) ArticleTitleSites and mechanisms of action of neuropeptides on canine gastric motility differ in vivo and in vitro Life Sci 33 817–25 Occurrence Handle10.1016/0024-3205(83)90619-7 Occurrence Handle1:CAS:528:DyaL3sXkvF2rsrw%3D Occurrence Handle6193389
HM Jennewein H Hummelt R Siewent F Waldeck (1975) ArticleTitleThe motor-stimulating effect of natural motilin on the lower esophageal sphincter, fundus, antrum and duodenum in dogs Digestion 13 246–50 Occurrence Handle1:CAS:528:DyaE28XlsVGgsQ%3D%3D Occurrence Handle1205010 Occurrence Handle10.1159/000197714
U Strunz W Domschke P Mitznegg S Domschke E Schubert E Wunsch et al. (1975) ArticleTitleAnalysis of the motor effects of 13-norleucine motilin on the rabbit, guinea pig, rat, and human alimentary tract in vitro Gastroenterology 68 1485–91 Occurrence Handle1:CAS:528:DyaE2MXlsFymsbg%3D Occurrence Handle1132629
V Annese G Lombardi V Frusciante U Germani A Andriulli G Bassotti (1997) ArticleTitleCisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin-dependent) diabetes mellitus Aliment Pharmacol Ther 11 599–603 Occurrence Handle10.1046/j.1365-2036.1997.00177.x Occurrence Handle1:CAS:528:DyaK2sXks1egt7g%3D Occurrence Handle9218089
GV Assche I Depoortere T Thijs L Missiaen F Penninckx H Takanashi et al. (2001) ArticleTitleContractile effects and intracellular Ca2+ signaling induced by motilin and erythromycin in the circular smooth muscle of human colon Neurogastroenterol Motil 13 27–35 Occurrence Handle10.1046/j.1365-2982.2001.00237.x Occurrence Handle11169123
BJ Kendall A Chakravarti E Kendall I Soykan W McCallum (1997) ArticleTitleThe effect of intravenous erythromycin on solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis Aliment Pharmacol Ther 11 381–5 Occurrence Handle10.1046/j.1365-2036.1997.148324000.x Occurrence Handle1:CAS:528:DyaK2sXjt1entbs%3D Occurrence Handle9146779
S Shyam NB Sharma CM Satish (1995) ArticleTitleEffect of oral erythromycin on colonic transit in patients with idiopathic constipation Dig Dis Sci 40 2446–9 Occurrence Handle10.1007/BF02063252
T Minami H Nishibayashi Y Shinomura Y Matsuzawa (1996) ArticleTitleEffects of erythromycin in chronic idiopathic intestinal pseudo-obstruction J Gastroenterol 31 855–9 Occurrence Handle10.1007/BF02358615 Occurrence Handle1:STN:280:DyaK2s7nvFeltA%3D%3D Occurrence Handle9027652
JS Jameson J Rogers JJ Misiewiez AH Raimundo MM Henry (1992) ArticleTitleOral or intravenous erythromycin has no effects on human distal colonic motility Aliment Pharmacol Ther 6 589–95 Occurrence Handle1:CAS:528:DyaK3sXlvFM%3D Occurrence Handle1420750 Occurrence Handle10.1111/j.1365-2036.1992.tb00573.x
J Janssens G Vantrappen TL Peeters (1983) ArticleTitleThe activity front of the migrating motor complex of the human stomach but not of the small intestine is motilin-dependent Regul Pept 6 363–9 Occurrence Handle10.1016/0167-0115(83)90265-3 Occurrence Handle1:CAS:528:DyaL3sXlsFals7s%3D Occurrence Handle6635258
J Huang Zhou Huiping S Mahavadi W Sriwai V Lyall KS Murthy (2005) ArticleTitleSignaling pathways mediating gastrointestinal smooth muscle contraction and MLC 20 phosphorylation by motilin receptors Am J Physiol 288 G23–31 Occurrence Handle1:CAS:528:DC%2BD2MXhtVGisrY%3D
L Xu I Depoortere C Tomasetto M Zandecki M Tang J Timmermans et al. (2005) ArticleTitleEvidence for the presence of motilin, ghrelin, and the motilin and ghrelin receptor in neurons of the myenteric plexus Regul Pept 124 119–25 Occurrence Handle10.1016/j.regpep.2004.07.022 Occurrence Handle1:CAS:528:DC%2BD2cXpslGmsb8%3D Occurrence Handle15544849
NJ Talley M Verlinden W Snape JA Beker P Ducrotte A Dettmer et al. (2000) ArticleTitleFailure 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 Aliment Pharmacol Ther 14 1653–61 Occurrence Handle10.1046/j.1365-2036.2000.00868.x Occurrence Handle1:CAS:528:DC%2BD3MXkvVOrtA%3D%3D Occurrence Handle11121915
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Takeshita, E., Matsuura, B., Dong, M. et al. Molecular characterization and distribution of motilin family receptors in the human gastrointestinal tract. J Gastroenterol 41, 223–230 (2006). https://doi.org/10.1007/s00535-005-1739-0
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DOI: https://doi.org/10.1007/s00535-005-1739-0