Motilin: Towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists

British Journal of Pharmacology

Volumn 170, Issue 7, 2013, Pages 1323-1332

  Sanger, G J ^a   Wang, Y ^a   Hobson, A ^b   Broad, J ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b Princess Grace Hospital   (United Kingdom)

Author keywords

gastrointestinal; ghrelin; motilin; neuropharmacology; translational sciences

Indexed keywords

ALEMCINAL; BMS 591348; CAMICINAL; ERYTHROMYCIN; GHRELIN RECEPTOR; GHRELIN RECEPTOR AGONIST; HORMONE RECEPTOR STIMULATING AGENT; MITEMCINAL; MOTILIN; MOTILIN RECEPTOR; RQ 00201894; TZP 201; UNCLASSIFIED DRUG; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; GASTROINTESTINAL AGENT; HORMONE RECEPTOR; NEUROPEPTIDE RECEPTOR;

ABDOMINAL CRAMP; BEDTIME DOSAGE; CACHEXIA; CALCIUM SIGNALING; CHOLINERGIC ACTIVITY; DESENSITIZATION; DIET RESTRICTION; DOSE RESPONSE; DRUG TREATMENT FAILURE; DYSPEPSIA; ENTEROPATHY; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL MOTILITY; HORMONE BLOOD LEVEL; HORMONE RELEASE; HUMAN; IMMUNOREACTIVITY; INTESTINE CONTRACTION; INTESTINE DISTENSION; INTESTINE PSEUDOOBSTRUCTION; LOW DRUG DOSE; MYENTERIC PLEXUS; NAUSEA; NONHUMAN; NUTRITIONAL INTOLERANCE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REPEATED DRUG DOSE; REVIEW; SIDE EFFECT; STOMACH EMPTYING; STOMACH PARESIS; TACHYPHYLAXIS; AGONISTS; ANIMAL; CHEMISTRY; DRUG DESIGN; DRUG EFFECTS; GASTROINTESTINAL DISEASES; GASTROINTESTINAL TRACT; INNERVATION; INTESTINE INNERVATION; METABOLISM; PATHOPHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; DRUG DESIGN; ENTERIC NERVOUS SYSTEM; ERYTHROMYCIN; GASTROINTESTINAL AGENTS; GASTROINTESTINAL DISEASES; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRACT; HUMANS; MOTILIN; NEUROTRANSMITTER AGENTS; RECEPTORS, GASTROINTESTINAL HORMONE; RECEPTORS, NEUROPEPTIDE; SIGNAL TRANSDUCTION;

EID: 84885470949     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12075     Document Type: Review

References (102)

1. Abu-Gharbieh E, Vasina V, Poluzzi E, De Ponti F, (2004). Antibacterial macrolides: a drug class with a complex pharmacological profile. Pharmacol Res 50: 211-222.
2. Ang DC, Nicolai H, Vos R, Berghe PV, Sifrim D, Depoortere I, et al. (2008). Gastric phase 3 is a hunger signal in the interdigestive state in man. Gastroenterology 134 (4 Suppl. 1): A-314 (abstract).
3. Ashitani J, Matsumoto N, Nakazato M, (2009). Ghrelin and its therapeutic potential for cachectic patients. Peptides 30: 1951-1956.
4. Bailey CP, Smith FL, Kelly E, Dewey WL, Henderson G, (2006). How important is protein kinase C in mu-opioid receptor desensitization and morphine tolerance? Trends Pharmacol Sci 27: 558-565.
5. Bassil A, Murray C, Dass NM, Muir A, Sanger GJ, (2005). Prokineticin-2, motilin, ghrelin and metoclopramide: prokinetic utility in mouse stomach and colon. Eur J Pharmacol 524: 138-144.
6. Bassotti G, Chiarioni G, Vantini I, Morelli A, Whitehead WE, (1998). Effect of different doses of erythromycin on colonic motility in patients with slow transit constipation. Z Gastroenterol 36: 209-213.
7. Boivin M, Bradette M, Raymond MC, Riberdy-Poitras M, Poitras P, (1992a). Mechanisms for post-prandial release of motilin in humans. Dig Dis Sci 37: 1562-1568.
8. Boivin M, Riberdy M, Raymond MC, Trudel L, Poitras P, (1992b). Motilin and the post-prandial motility of the antrum. Can J Physiol Pharmacol 70: 1491-1495.
9. Boivin MA, Carey MC, Levy H, (2003). Erythromycin accelerates gastric emptying in a dose-response manner in healthy subjects. Pharmacotherapy 23: 5-8.
10. Broad J, Mukherjee S, Samadi M, Martin JE, Dukes GE, Sanger GJ, (2012). Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists. Br J Pharmacol 167: 763-774.
11. Broad J, Sanger GJ, (2012). The antibiotic azithromycin is a motilin receptor agonist in human stomach: Comparison with erythromycin. Br J Pharmacol, doi: 10.1111/bph.12077.
12. Brown JC, Johnson LP, Magee DF, (1966). Effect of duodenal alkalinization on gastric motility. Gastroenterology 50: 333-339.
13. Brown JC, Cook MA, Dryburgh JR, (1973). Motilin, a gastric motor activity stimulating polypeptide: the complete amino acid sequence. Can J Biochem 51: 533-537.
14. Camilleri M, Papathanasopoulos A, Odunsi ST, (2009). Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol 6: 343-352.
15. Carbonell N, Pauwels A, Serfaty L, Boelle PY, Becquemont L, Poupon R, (2006). Erythromycin infusion prior to endoscopy for acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Am J Gastroenterol 101: 1211-1215.
16. Carreras CW, Claypool M, Santi DV, Schuukes J, Peeters TL, Johnson RG, (2004). Tachyphylaxis assays for motilin agonist drug development. Gastroenterology 126 (4 Suppl. 2): A-276.
17. Chapman M, Fraser R, Nguyen N, Deane A, O'Connor S, Richards D, et al. (2011). The effect of GSK962040, a selective motilin agonist, on gastric emptying in critically ill patients with enteral feed intolerance. Crit Care Med 39: 195 (abstract).
18. Christofides ND, (1978). Importance of the jejunal hormone motilin. J Clin Pathol 33 (Suppl. 8): 51-57.
19. Costa A, De Ponti F, Gibelli G, Crema F, d'Angelo L, (1997). In vivo characterisation of the colonic prokinetic effect of erythromycin in the rabbit. Pharmacology 54: 64-75.
20. Coulie B, Tack J, Peeters T, Janssens J, (1998). Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans. Gut 43: 395-400.
21. Cuomo R, Vandaele P, Coulie B, Peeters T, Depoortere I, Janssens J, et al. (2006). Influence of motilin on gastric fundus tone and on meal-induced satiety in man: role of cholinergic pathways. Am J Gastroenterol 101: 804-811.
22. Dass NB, Hill J, Muir A, Testa T, Wise A, Sanger GJ, (2003). The rabbit motilin receptor: molecular characterisation and pharmacology. Br J Pharmacol 140: 948-954.
23. De Ponti F, Poluzzi E, Montanaro N, (2000). QT-interval prolongation by non-cardiac drugs: lessons to be learned from recent experience. Eur J Clin Pharmacol 56: 1-18.
24. Depoortere I, Peeters TL, (1995). Transduction mechanism of motilin and motilides in rabbit duodenal smooth muscle. Regul Pept 55: 227-235.
25. Depoortere I, Van Assche G, Peeters TL, (1997). Distribution and subcellular localization of motilin binding sites in the rabbit brain. Brain Res 777: 103-109.
26. Depoortere I, Van Assche G, Thijs T, Geboes K, Peeters TL, (1999). Differential changes in ACh-, motilin-, substance P-, and K(+)-induced contractility in rabbit colitis. Am J Physiol 277: G61-G68.
27. Dhir R, Richter JE, (2004). Erythromycin in the short- and long-term control of dyspepsia symptoms in patients with gastroparesis. J Clin Gastroenterol 38: 237-242.
28. DiBaise JK, Quigley EM, (1999). Efficacy of prolonged administration of intravenous erythromycin in an ambulatory setting as treatment of severe gastroparesis: one centre's experience. J Clin Gastroenterol 28: 131-134.
29. Dukes GE, Barton M, Dewit O, Hicks K, Vasist L, Van Hecken A, et al. (2009). Pharmacokinetics, safety/tolerability, and effect on gastric emptying of the oral motilin receptor agonist, GSK962040, in healthy male and female volunteers. Neurogastroenterol Motil 21 (Suppl. 1): 84.
30. Dukes GE, Barton M, Dewit O, Stephens K, Vasist L, Young M, et al. (2010). Safety/tolerability, pharmacokinetics (PK), and effect on gastric emptying(GE) with 14-days repeat oral dosing of the motilin receptor agonist, GSK962040, in healthy male and female volunteers. Neurogastroenterol Motil 22 (Suppl. 1): 14-15.
31. Emmanuel AV, Shand AG, Kamm MA, (2004). Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive response. Alim Pharmacol Ther 19: 687-694.
32. Feighner SD, Tan CP, McKee KK, Palyha OC, Hreniuk DL, Pong SS, et al. (1999). Receptor for motilin identified in the human gastrointestinal system. Science 284: 2184-2188.
33. Feng X, Peeters TL, Tang M, (2007). Motilin activates neurons in the rat amygdala and increases gastric motility. Peptides 28: 625-631.
34. Folwaczny C, Chang JK, Tschöp M, (2001). Ghrelin and motilin: two sides of one coin? Eur J Endocrinol 144: R1-R3.
35. Fukudo S, Suzuki J, (1987). Colonic motility, autonomic function, and gastrointestinal hormones under psychological stress on irritable bowel syndrome. Tohoku J Exp Med 151: 373-385.
36. Furness JB, Clark MJ, Wright T, Bertrand PP, Bornstein JC, Verlinden M, (1999). An action of erythromycin in the intestine that is not mediated via motilin receptors. Clin Exp Pharmacol Physiol 26: 100-104.
37. Gadenstätter M, Prommegger R, Klinger A, Schwelberger H, Weiss HG, Glaser K, et al. (2001). Alterations of gut neuropeptides in gastroesophageal reflux disease are resolved after antireflux surgery. Am J Surg 180: 483-487.
38. Gonlachanvit S, Hsu CW, Boden GH, Knight LC, Maurer AH, Fisher RS, et al. (2003). Effect of altering gastric emptying on postprandial plasma glucose concentrations following a physiologic meal in type-II diabetic patients. Dig Dis Sci 48: 488-497.
39. Hawkyard CV, Koerner RJ, (2007). The use of erythromycin as a gastrointestinal prokinetic agent in adult critical care: benefits versus risks. J Antimicrobial Chemother 59: 347-358.
40. He J, Irwin DM, Chen R, Zhang Y-P, (2010). Stepwise loss of motilin and its specific receptor genes in rodents. J Mol Endocrinol 44: 37-44.
41. Hellström PM, Tack J, Barton ME, Stephens KE, Vasist LS, Richards DB, et al. (2011). A double-blind, randomized placebo-controlled phase II study of the pharmacokinetics of single doses of the motilin agonist GSK962040, in patients with type I diabetes mellitus (TIDM) and gastroparesis. Gastroenterology 140: S183.
42. Higuchi Y, Nishimura J, Kanaide H, (1994). Motilin induces the endothelium-dependeent relaxation of smooth muscle and the elevation of cytosolic calcium in endothelial cells in situ. Biochem Biophys Res Commun 202: 346-353.
43. Husebye E, (1999). The patterns of small bowel motility: physiology and implications in organic disease and functional disorders. Neurogastroenterol Motil 11: 141-161.
44. Itoh Z, Nakaya M, Suzuki T, Arai H, Wakabayashi K, (1984). Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Physiol 247: G688-G694.
45. 13]motilin in dogs in vivo and in vitro. Can J Physiol Pharmacol 76: 1103-1109.
46. Jameson JS, Rogers J, Misiewicz JJ, Raimundo AH, Henry MM, (1992). Oral or intravenous erythromycin has no effect on human distal colonic motility. Alim Pharmacol Ther 6: 589-595.
47. Jarvie EM, North Laidler V, Corcoran S, Bassil A, Sanger GJ, (2007). Differences between the abilities of tegaserod and motilin receptor agonists to stimulate gastric motility in vitro. Br J Pharmacol 150: 455-462.
48. Jonsson BH, Hellström PM, (2000). Motilin- and neuropeptide Y-like immunoreactivity in a psychophysiological stress experiment on patients with functional dyspepsia. Integr Physiol Behav Sci 35: 256-265.
49. Kamerling IM, van Haarst AD, Burggraaaf J, Schoemaker RC, de, Kam ML, Heinzerling H, et al. (2004). Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function. Br J Clin Pharmacol 57: 393-401.
50. Kusano M, Sekiguchi T, Kawamura O, Kikuchi K, Miyazaki M, Tsunoda T, et al. (1997). Further classification of dysmotility-like dyspepsia by interdigestive gastroduodenal manometry and plasma motilin level. Am J Gastroenterol 92: 481-484.
51. Lamian V, Rich A, Ma Z, Li J, Seethala R, Gordon D, et al. (2006). Characterization of agonist-induced motilin receptor trafficking and its implications for tachyphylaxis. Mol Pharmacol 69: 109-118.
52. Lee KY, Chang TM, Chey WY, (1983). Effect of rabbit antimotilin serum on myoelectric activity and plasma motilin concentration in fasting dog. Am J Physiol 245: G547-G553.
53. Leming S, Broad J, Cozens SJ, Otterson M, Winchester W, Lee K, et al. (2011). GSK962040: a small molecule motilin receptor agonist which increases gastrointestinal motility in conscious dogs. Neurogastroenterol Motil 23: 958-964.
54. Levy H, Hayes J, Boivin M, Tomba T, (2004). Transpyloric feeding tube placement in critically ill patients using electromyogram and erythromycin infusion. Chest 125: 587-591.
55. Li JJ, Chao H-G, Wang H, Tino JA, Lawrence RM, Ewing WR, et al. (2004). Discovery of a potent and novel motilin agonist. J Med Chem 47: 1704-1708.
56. McCallum RW, Cynshi O, Investigator Team (2007). Efficacy of mitemcinal, a motilin receptor agonist, on gastrointestinal symptoms in patients with symptoms suggesting diabetic gastropathy: a randomized, multi-centere, placebo-controlled trial. Aliment Pharmacol Ther 26: 107-116.
57. Maganti K, Onyemere K, Jones MP, (2003). Oral erythromycin and symptomatic relief of gastroparesis: a systematic review. Am J Gastroenterol 98: 259-263.
58. Maguire JJ, Kuc RE, Davenport AP, (2004). Motilin mediates vasoconstriction in human coronary artery in vitro. Proc Br Pharmacol Soc. Available at: http://www.pa2online.org/Vol2Issue2abst116P.html (accessed 4 January 2013).
59. Mangoni AA, Close JC, Rodriguez S, Sherwood RA, Bryant CA, Swift CG, et al. (2004). Acute hypotensive effects of oral cisapride and erythromycin in healthy subjects. Br J Clin Pharmacol 58: 223-224.
60. Matthijs G, Peeters TL, Vantrappen G, (1989). The role of intracellular calcium stores in motilin induced contractions of the longitudinal muscle of the rabbit duodenum. Naunyn Schmiedebergs Arch Pharmacol 339: 332-339.
61. Miller P, Roy A, St-Pierre S, Dagenais M, Lapointe R, Poitras P, (2000). Motilin receptors in the human antrum. Am J Physiol 278: G18-G23.
62. Mitselos A, Vanden Berghe P, Peeters TL, Depoortere I, (2008). Differences in motilin receptor desensitization after stimulation with motilin or motilides are due to alternative receptor trafficking. Biochem Pharmacol 75: 1115-1128.
63. Mochiki E, Inui A, Satoh M, Mizumoto A, Itoh Z, (1997). Motilin is a biosignal controlling cyclic release of pancreatic polypeptide via the vagus in fasted dogs. Am J Physiol 272: G224-G232.
64. Mömke S, Sickinger M, Rehage J, Doll K, Distl O, (2012). Transcription factor binding site polymorphism in the motilin gene associated with left-sided displacement of the abomasum in German Holstein cattle. PLoS ONE 7: e35562. doi: 10.1371/journal.pone.0035562.
65. Nakajima H, Mochiki E, Zietlow A, Ludwig K, Takahashi T, (2010). Mechanism of interdigestive migrating motor complex in conscious dogs. J Gastroenterol 45: 506-514.
66. Nguyen NQ, Mangoni AA, Fraser RJ, Chapman M, Bryant L, Burgstad C, et al. (2006). Prokinetic therapy with erythromycin has no significant impact on blood pressure and heart rate in critically ill patients. Br J Clin Pharmacol 63: 498-500.
67. Nieuwenhuijs VB, van Duijvenbode-Beumer H, Verheem A, Visser MR, Verhoef J, Gooszen HG, et al. (1999). The effects of ABT-229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats. Eur J Clin Invest 29: 33-40.
68. Nunoi H, Matsuura B, Utsunomiya S, Ueda T, Miyake T, Furukawa S, et al. (2012). A relationship between motilin and growth hormone secretagogue receptors. Regul Pept 176: 28-35.
69. Oei J, Lui K, (2001). A placebo-controlled trial of low-dose erythromycin to promote feed tolerance in preterm infants. Acta Paediatr 90: 904-908.
70. Ohno T, Mochiki E, Kuwano H, (2010). The roles of motilin and ghrelin in gastrointestinal motility. Int J Pept 2010: 1-6.
71. Ohshiro H, Nonaka M, Ichikawa K, (2008). Molecular identification and characterization of the dog motilin receptor. Regul Pept 146: 80-87.
72. Okudaira T, Kotegawa T, Imai H, Tsutsumi K, Nakano S, Ohashi K, (2007). Effect of the treatment period with erythromycin on cytochrome P450 3A activity in humans. J Clin Pharmacol 47: 871-876.
73. Peeters T, Matthijs G, Depoortere I, Cachet T, Hoogmartens J, Vantrappen G, (1989). Erythromycin is a motilin receptor agonist. Am J Physiol 257: G470-G474.
74. Peeters TL, (2006). Potential of ghrelin as a therapeutic approach for gastrointestinal motility disorders. Curr Opin Pharmacol 6: 553-558.
75. Ritz MA, Chapman MJ, Fraser RJ, Finnis ME, Butler RN, Cmielewski P, et al. (2005). Erythromycin dose of 70 mg accelerates gastric emptying as effectively as 200 mg in the critically ill. Intensive Care Med 31: 949-954.
76. Sanger GJ, (2008). Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases. Drug Discov Today 13: 234-239.
77. Sanger GJ, Alpers D, (2008). Development of drugs for gastrointestinal motor disorders: translating science to clinical need. Neurogastroenterol Motil 20: 177-184.
78. Sanger GJ, Lee K, (2008). Hormones of the gut-brain axis as targets for the treatment of upper GI disorders. Nat Rev Drug Discov 7: 241-254.
79. Sanger GJ, Westaway SM, Barnes AA, MacPherson DT, Muir AI, Jarvie EM, et al. (2009). GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil 21: 657-666.
80. Sanger GJ, Holbrook JD, Andrews PLR, (2011). The translational value of rodent gastrointestinal functions: a cautionary tale. Trends Pharmacol Sci 32: 402-409.
81. 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.
82. Shay H, Gershon-Cohen J, (1935). Experimental studies in gastric physiology in man: the mechanism of gastric evacuation after partial gastrectomy as demonstrated roentgenologically. Am J Dig Dis 2: 608-613.
83. Simrén M, Abrahamsson H, Bjornsson ES, (2001). An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome. Gut 48: 20-27.
84. Simrén M, Bjornsson ES, Abrahamsson H, (2005). High interdigestive and postprandial motilin levels with the irritable bowel syndrome. Neurogastroenterol Motil 17: 51-57.
85. Sjölund K, Ekman R, Wierup N, (2010). Covariation of plasma ghrelin and motilin in irritable bowel syndrome. Peptides 31: 1109-1112.
86. Suzuki H, Mochiki E, Haga N, Satoh M, Mizumoto A, Itoh Z, (1998). Motilin controls cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs. Am J Physiol 274: G87-G95.
87. Tack J, Peeters T, (2001). What comes after macrolides and other motilin stimulants? Gut 49: 317-318.
88. Takahashi N, Koba N, Yamamoto T, Sudo M, (2010). Characterization of a novel, potent and selective small molecule motilin receptor agonist, RQ-00201894. Gastroenterology 138 (5 Suppl. 1): S-713.
89. Takanashi H, Cynshi O, (2009). Motilides: a long and winding road: lessons from mitemcinal (GM-611) on diabetic gastroparesis. Regul Pept 155: 18-23.
90. Takeshita E, Matsuura B, Dong M, Miller LJ, Matsui H, Onji M, (2006). Molecular characterisation and distribution of motilin family receptors in the human gastrointestinal tract. J Gastroenterol 41: 223-230.
91. Talley NJ, Verlinden M, Geenen D, Hogan R, Riff D, McCallum R, et al. (2001). Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial. Gut 49: 395-401.
92. Ter Beek WP, Möller ESM, van den, Berg M, Meijer MJ, Biemond I, Lamers CB, (2008). Motilin receptor expression in smooth muscle, myenteric plexus, and mucosa of human inflamed and noninflamed intestine. Inflamm Bowel Dis 14: 612-619.
93. Thielemans L, Depoortere I, Perret J, Robberecht P, Liu Y, Thijs T, et al. (2005). Desensitization of the human motilin receptor by motilides. J Pharmacol Exp Ther 313: 1397-1405.
94. Thomas H, Chen C, Marsault E, (2007). The motilin receptor antagonist TZP-201 is highly effective in the control of irinotecan induced diarrhea in beagle dogs. Neurogastroenterol Motil 19 (Suppl. 3): 35 (abstract).
95. 13]motilin in the isolated rabbit gastric antrum. Eur J Pharmacol 337: 267-274.
96. Venkatasubramani N, Rudolph CD, Sood MR, (2008). Erythromycin lacks colon prokinetic effect in children with functional gastrointestinal disorders: a retrospective study. BMC Gastroenterol 8: 38.
97. Westaway SM, Sanger GJ, (2009). The identification and rationale for drugs which act at the motilin receptor. Prog Med Chem 48: 31-80.
98. Wierup N, Björkqvist M, Westrom B, Pierzynowski S, Sundler F, Sjölund K, (2007). Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine. J Clin Endocrinol Metab 92: 3573-3581.
99. Wilmer A, Tack J, Coremans G, Janssens J, Peeters T, Vantrappen G, (1993). 5-hydroxytryptamine-3 receptors are involved in the initiation of gastric phase-3 motor activity in humans. Gastroenterology 105: 773-780.
100. Yanaihara C, Sato H, Yanaihara N, Naruse S, Forssmann WG, Helmstaedter V, et al. (1978). Motilin-, substance P- and somatostatin-like immunoreactivities in extracts from dog, tupaia and monkey brain and GI tract. Adv Exp Med Biol 106: 269-283.
101. Zeitlow AM, Ludwig KA, Takahashi T, (2010). Association between plasma ghrelin and motilin levels during interdigestive MMC cycle in conscious dogs. Gastroenterology 138 (5 Suppl. 1): S-737.
102. Zhao DM, Xue HH, Chida K, Suda T, Oki Y, Kanai M, et al. (2000). Effect of erythromycin on ATP-induced intracellular calcium response in A549 cells. Am J Physiol 278: L726-L736.