Skip to main content
Gut logoLink to Gut
. 1998 Jun;42(6):830–835. doi: 10.1136/gut.42.6.830

Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

Y Luiking 1, T Peeters 1, M Stolk 1, V Nieuwenhuijs 1, P Portincasa 1, I Depoortere 1, Henegou G P van Berge 1, L Akkermans 1
PMCID: PMC1727155  PMID: 9691922

Abstract

Background—Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying. 
Aims—To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans. 
Methods—After an overnight fast, eight healthy men received increasing intravenous doses of Leu13-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography. 
Results—Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, ,8 and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p<0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p<0.05). 
Conclusions—Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state. 



Keywords: motilin; gall bladder; antrum; motility; ultrasonography

Full Text

The Full Text of this article is available as a PDF (121.8 KB).

Figure 1 .

Figure 1

Plasma motilin levels before and during infusion of stepwise increased doses of motilin (means (SEM)). Horizontal bars show the motilin dose.

Figure 2 .

Figure 2

Effect of motilin (closed circles) versus placebo (saline; open squares) infusion on gall bladder volume (mean (SEM)). Gall bladder volumes are expressed as percentages of the baseline volume. Horizontal bars show the motilin dosage. p<0.05 for motilin versus placebo.

Figure 3 .

Figure 3

Antral contraction frequency (median and interquartile range) during the 20 minute period before infusion, the 80 minute period of infusion, and the 20 minute period after infusion of motilin (shaded column) and of placebo (open column).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bolondi L., Bortolotti M., Santi V., Calletti T., Gaiani S., Labò G. Measurement of gastric emptying time by real-time ultrasonography. Gastroenterology. 1985 Oct;89(4):752–759. doi: 10.1016/0016-5085(85)90569-4. [DOI] [PubMed] [Google Scholar]
  2. Bormans V., Peeters T. L., Janssens J., Pearce D., Vandeweerd M., Vantrappen G. In man, only activity fronts that originate in the stomach correlate with motilin peaks. Scand J Gastroenterol. 1987 Sep;22(7):781–784. doi: 10.3109/00365528708991914. [DOI] [PubMed] [Google Scholar]
  3. Brown J. C., Mutt V., Dryburgh J. R. The further purification of motilin, a gastric motor activity stimulating polypeptide from the mucosa of the small intestine of hogs. Can J Physiol Pharmacol. 1971 May;49(5):399–405. doi: 10.1139/y71-047. [DOI] [PubMed] [Google Scholar]
  4. Catnach S. M., Fairclough P. D., Trembath R. C., O'Donnell L. J., McLean A. M., Law P. A., Wickham J. E. Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones. Gastroenterology. 1992 Jun;102(6):2071–2076. doi: 10.1016/0016-5085(92)90334-u. [DOI] [PubMed] [Google Scholar]
  5. Dooley C. P., Di Lorenzo C., Valenzuela J. E. Variability of migrating motor complex in humans. Dig Dis Sci. 1992 May;37(5):723–728. doi: 10.1007/BF01296429. [DOI] [PubMed] [Google Scholar]
  6. Everson G. T., Braverman D. Z., Johnson M. L., Kern F., Jr A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology. 1980 Jul;79(1):40–46. [PubMed] [Google Scholar]
  7. Fiorucci S., Bosso R., Morelli A. Erythromycin stimulates gallbladder emptying and motilin release by atropine-sensitive pathways. Dig Dis Sci. 1992 Nov;37(11):1678–1684. doi: 10.1007/BF01299858. [DOI] [PubMed] [Google Scholar]
  8. Fiorucci S., Distrutti E., Quintieri A., Sarpi L., Spirchez Z., Gulla N., Morelli A. L-arginine/nitric oxide pathway modulates gastric motility and gallbladder emptying induced by erythromycin and liquid meal in humans. Dig Dis Sci. 1995 Jun;40(6):1365–1371. doi: 10.1007/BF02065553. [DOI] [PubMed] [Google Scholar]
  9. Fiorucci S., Santucci L., Morelli A. 5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin. Dig Dis Sci. 1993 Dec;38(12):2236–2240. doi: 10.1007/BF01299902. [DOI] [PubMed] [Google Scholar]
  10. Fiorucci S., Scionti L., Bosso R., Desando A., Bottini P., Marino C., Morelli A. Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin. Dig Dis Sci. 1992 Nov;37(11):1671–1677. doi: 10.1007/BF01299857. [DOI] [PubMed] [Google Scholar]
  11. Hall K. E., Greenberg G. R., El-Sharkawy T. Y., Diamant N. E. Relationship between porcine motilin-induced migrating motor complex-like activity, vagal integrity, and endogenous motilin release in dogs. Gastroenterology. 1984 Jul;87(1):76–85. [PubMed] [Google Scholar]
  12. Itoh Z., Takahashi I. Periodic contractions of the canine gallbladder during the interdigestive state. Am J Physiol. 1981 Feb;240(2):G183–G189. doi: 10.1152/ajpgi.1981.240.2.G183. [DOI] [PubMed] [Google Scholar]
  13. Jebbink M. C., Masclee A. A., van der Kleij F. G., Schipper J., Rovati L. C., Jansen J. B., Lamers C. B. Effect of loxiglumide and atropine on erythromycin-induced reduction in gallbladder volume in human subjects. Hepatology. 1992 Oct;16(4):937–942. doi: 10.1002/hep.1840160414. [DOI] [PubMed] [Google Scholar]
  14. Kraglund K., Hjermind J., Jensen F. T., Stødkilde-Jørgensen H., Oster-Jørgensen E., Pedersen S. A. Gallbladder emptying and gastrointestinal cyclic motor activity in humans. Scand J Gastroenterol. 1984 Oct;19(7):990–994. [PubMed] [Google Scholar]
  15. Kusano M., Sekiguchi T., Nishioka T., Kawamura O., Kikuchi K., Matsuzaki T., Horikoshi T., Kobayashi S. The relationship between interdigestive gallbladder and gastroduodenal motility in man. Gastroenterol Jpn. 1990 Oct;25(5):568–574. doi: 10.1007/BF02779356. [DOI] [PubMed] [Google Scholar]
  16. Lee K. Y., Park H. J., Chang T. M., Chey W. Y. Cholinergic role on release and action of motilin. Peptides. 1983 May-Jun;4(3):375–380. doi: 10.1016/0196-9781(83)90149-3. [DOI] [PubMed] [Google Scholar]
  17. Marzio L., Neri M., Capone F., Di Felice F., De Angelis C., Mezzetti A., Cuccurullo F. Gallbladder contraction and its relationship to interdigestive duodenal motor activity in normal human subjects. Dig Dis Sci. 1988 May;33(5):540–544. doi: 10.1007/BF01798354. [DOI] [PubMed] [Google Scholar]
  18. Masclee A. A., Ledeboer M. L., Gielkens H. G., van der Kleij F. G., Jebbink M. C., Lamers C. B. Effect of erythromycin on gallbladder emptying in patients with antrectomy or truncal vagotomy. Am J Gastroenterol. 1995 Jun;90(6):973–977. [PubMed] [Google Scholar]
  19. Mitznegg P., Bloom S. R., Domschke W., Domschke S., Wuensch E., Demling L. Pharmacokinetics of motilin in man. Gastroenterology. 1977 Mar;72(3):413–416. [PubMed] [Google Scholar]
  20. Mochiki E., Satoh M., Tamura T., Haga N., Suzuki H., Mizumoto A., Sakai T., Itoh Z. Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog. Gastroenterology. 1996 Dec;111(6):1456–1464. doi: 10.1016/s0016-5085(96)70006-9. [DOI] [PubMed] [Google Scholar]
  21. Nilsson B. I., Svenberg T., Tollström T., Hellström P. M., Samuelson K., Schnell P. O. Relationship between interdigestive gallbladder emptying, plasma motilin and migrating motor complex in man. Acta Physiol Scand. 1990 May;139(1):55–61. doi: 10.1111/j.1748-1716.1990.tb08897.x. [DOI] [PubMed] [Google Scholar]
  22. Owyang C., Achem-Karam S. R., Vinik A. I. Pancreatic polypeptide and intestinal migrating motor complex in humans. Effect of pancreaticobiliary secretion. Gastroenterology. 1983 Jan;84(1):10–17. [PubMed] [Google Scholar]
  23. Parkman H. P., Pagano A. P., Vozzelli M. A., Ryan J. P. Gastrokinetic effects of erythromycin: myogenic and neurogenic mechanisms of action in rabbit stomach. Am J Physiol. 1995 Sep;269(3 Pt 1):G418–G426. doi: 10.1152/ajpgi.1995.269.3.G418. [DOI] [PubMed] [Google Scholar]
  24. Peeters T. L., Vantrappen G., Janssens J. Bile acid output and the interdigestive migrating motor complex in normals and in cholecystectomy patients. Gastroenterology. 1980 Oct;79(4):678–681. [PubMed] [Google Scholar]
  25. Peeters T. L., Vantrappen G., Janssens J. Fasting plasma motilin levels are related to the interdigestive motility complex. Gastroenterology. 1980 Oct;79(4):716–719. [PubMed] [Google Scholar]
  26. Portincasa P., Di Ciaula A., Palmieri V., Van Berge-Henegouwen G. P., Palasciano G. Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects. Eur J Clin Invest. 1995 Oct;25(10):746–753. doi: 10.1111/j.1365-2362.1995.tb01953.x. [DOI] [PubMed] [Google Scholar]
  27. Qvist N. Motor activity of the gallbladder and gastrointestinal tract as determinants of enterohepatic circulation. A scintigraphic and manometric study. Dan Med Bull. 1995 Nov;42(5):426–440. [PubMed] [Google Scholar]
  28. Qvist N., Oster-Jørgensen E., Pedersen S. A., Rasmussen L., Hovendal C., Holst J. J. Increases in plasma motilin follow each episode of gallbladder emptying during the interdigestive period, and changes in serum bile acid concentration correlate to plasma motilin. Scand J Gastroenterol. 1995 Feb;30(2):122–127. doi: 10.3109/00365529509093249. [DOI] [PubMed] [Google Scholar]
  29. Scott R. B., Diamant S. C., Greenburg G. R. Do motilin and pancreatic polypeptide regulate duodenal bile acid delivery? Can J Physiol Pharmacol. 1988 Dec;66(12):1499–1504. doi: 10.1139/y88-245. [DOI] [PubMed] [Google Scholar]
  30. Stolk M. F., van Erpecum K. J., Smout A. J., Akkermans L. M., Jansen J. B., Lamers C. B., Peeters T. L., vanBerge-Henegouwen G. P. Motor cycles with phase III in antrum are associated with high motilin levels and prolonged gallbladder emptying. Am J Physiol. 1993 Apr;264(4 Pt 1):G596–G600. doi: 10.1152/ajpgi.1993.264.4.G596. [DOI] [PubMed] [Google Scholar]
  31. Strunz U., Domschke W., Domschke S., Mitznegg P., Wünsch E., Jaeger E., Demling L. Gastroduodenal motor response to natural motilin and synthetic position 13-substituted motilin analogues: a comparative in vitro study. Scand J Gastroenterol. 1976;11(2):199–203. [PubMed] [Google Scholar]
  32. Svenberg T., Christofides N. D., Fitzpatrick M. L., Areola-Ortiz F., Bloom S. R., Welbourn R. B. Interdigestive biliary output in man: relationship to fluctuations in plasma motilin and effect of atropine. Gut. 1982 Dec;23(12):1024–1028. doi: 10.1136/gut.23.12.1024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Svenberg T., Nilsson I., Samuelson K., Welbourn R. D. Studies on the causal relationship between gall-bladder emptying and motilin release in man. Acta Chir Scand Suppl. 1984;520:59–61. [PubMed] [Google Scholar]
  34. Takahashi I., Honda R., Dodds W. J., Sarna S., Toouli J., Itoh Z., Chey W. Y., Hogan W. J., Greiff D., Baker K. Effect of motilin on the opossum upper gastrointestinal tract and sphincter of Oddi. Am J Physiol. 1983 Oct;245(4):G476–G481. doi: 10.1152/ajpgi.1983.245.4.G476. [DOI] [PubMed] [Google Scholar]
  35. Takahashi I., Suzuki T., Aizawa I., Itoh Z. Comparison of gallbladder contractions induced by motilin and cholecystokinin in dogs. Gastroenterology. 1982 Mar;82(3):419–424. [PubMed] [Google Scholar]
  36. Vantrappen G., Janssens J., Peeters T. L., Bloom S. R., Christofides N. D., Hellemans J. Motilin and the interdigestive migrating motor complex in man. Dig Dis Sci. 1979 Jul;24(7):497–500. doi: 10.1007/BF01489315. [DOI] [PubMed] [Google Scholar]
  37. Yokohata K., Kimura H., Ogawa Y., Naritomi G., Tanaka M. Biliary motility. Changes in detailed characteristics correlated to duodenal migrating motor complex and effects of morphine and motilin in dogs. Dig Dis Sci. 1994 Jun;39(6):1294–1301. doi: 10.1007/BF02093796. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES