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Erythromycin stimulates gallbladder emptying and motilin release by atropine-sensitive pathways

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Abstract

The effect of administering different doses of erythromycin on gallbladder emptying and plasma concentrations of immunoreactive motilin was investigated in healthy volunteers. Erythromycin was infused for 30 min at four different doses: 20, 50, 100, and 1000 mg/hr. Gallbladder volume was determined by ultrasound scanning every 10 min for 60 min. All doses, except 20 mg/hr, provoked a significant reduction in gallbladder volume (P<0.01). The gallbladder emptying peak occurred after 20 min infusion. It was approximately 40–45% of basal volume and 60–70% of the emptying observed after a standard meal. At 100 mg/hr, erythromycin caused a 2.5-fold increase in plasma motilin concentration, which reached a peak after 30 min infusion. Plasma motilin peaked following maximum gallbladder emptying in all subjects. To evaluate whether cholinergic pathways were implicated in the action of erythromycin, 100 mg/hr erythromycin was infused together with 6 μg/kg/hr atropine. Atropine inhibited both gallbladder emptying and motilin release (P<0.001). Infusion of 1 μg/kg/hr somatostatin had the same inhibitory effects (P<0.001). Our results suggest that atropine acts by inhibiting an erythromycin-activated cholinergic neural mechanism. Somatostatin could exert its inhibitory effect by blocking the release of acetylcholine from neural terminations.

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References

  1. Itoh Z, Nakaya M, Suzuki T, Arai H, Wakabayashi K: Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Physiol 247:G688-G694, 1984

    Google Scholar 

  2. Tomomasa T, Kuroumi T, Arai H, Wakabayashi K, Itoh Z: Erythromycin induces migrating motor complex in human gastrointestinal tract. Dig Dis Sci 31:157–161, 1986

    Google Scholar 

  3. Otterson MF, Sarna SK: Gastrointestinal motor effects of erythromycin. Am J Physiol 259:G355-G363, 1990

    Google Scholar 

  4. Itoh Z, Takeuchi S, Aizawa I, Mori K, Tanimoto T, Seino Y, Imura H, Yanaihara N: Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dog. Am J Dig Dis 23:929–935, 1978

    Google Scholar 

  5. Vantrappen G, Janssens J, Peters TL, Bloom SR, Cristofides ND, Hellemans J: Motilin and the interdigestive migrating motor complex in humans. Dig Dis Sci 24:497–500, 1979

    Google Scholar 

  6. Peeters TL, Matthijs G, Depoortere I, Cachet T, Hoogmartens J, Vantrappen G: Erythromycin is a motilin receptor agonist. Am J Physiol 257:G470-G474, 1989

    Google Scholar 

  7. Kondo Y, Torii K, Omura S, Itoh Z: Erythromycin and its derivatives with motilin-like biological activities inhibits the specific binding of125I-motilin to duodenal muscle. Biochem Biophys Res Commun 150:877–882, 1988

    Google Scholar 

  8. Itoh Z, Takahashi I: Periodic contractions of the canine gallbladder during the interdigestive state. Am J Physiol 240:G183-G189, 1981

    Google Scholar 

  9. Peeters TL, Vantrappen G, Jenssen J: Bile acid output and the interdigestive migrating motor complex in normals and in cholecystectomy patients. Gastroenterology 79:678–681, 1980

    Google Scholar 

  10. Marzio L, Neri M, Capone F, Di Felice F, De Angelis C, Mezzeti A, Cuccurullo F: Gallbladder contraction and its relationship to interdigestive duodenal motor activity in normal human subjects. Dig Dis Sci 33:540–544, 1988

    Google Scholar 

  11. Takahashi I, Suzuki T, Aizawa I, Itoh Z: Comparison of gallbladder contractions induced by motilin and cholecystokinin in dogs. Gastroenterology 82:419–424, 1982

    Google Scholar 

  12. Svenberg T, Nilsson T, Samuelson K, Welbourn RD: Studies on the causal relationship between gallbladder emptying and motilin release in man. Acta Chir Scand 520:59–61, 1984

    Google Scholar 

  13. Pomeranz IS, Davison JS, Shaffer EA:In vitro effects of pancreatic polypeptide and motilin on contractility of human gallbladder. Dig Dis Sci 28:539–544, 1983

    Google Scholar 

  14. Catnach SM, Trembath RC, Law P, O'Donnel LJD, McLean AM, Wickham JE, Fairclough PD: Erythromycin a novel prokinetic agent for the gallbladder. Gastroenterology 98:245, 1990 (abstract)

    Google Scholar 

  15. Inatomi H, Satoh H, Maki Y, Hashimoto H, Itoh Z, Omura S: An erythromycin derivative, erythromycin-523, induces motilin-like gastrointestinal motility in dogs. J Pharmacol Exp Ther 254:940–944, 1990

    Google Scholar 

  16. Sarna SK: Cyclic motor activity, migrating motor complex: 1985. Gastroenterology 89:894–913, 1984

    Google Scholar 

  17. Bueno L, Fioramonti J, Rayner V, Ruckebusch Y: Effects of motilin, somatostatin, and pancreatic polypeptide on the migrating myoelectric complex in pig and dog. Gastroenterology 82:1395–1402, 1982

    Google Scholar 

  18. Ryan JP: Motility of the gallbladder and biliary tree.In Physiology of the Gastrointestinal Tract. LR Johnson (ed). New York, Raven Press, 1987, pp 695–721

    Google Scholar 

  19. Mori K, Seino Y, Itoh Z: Motilin release by intravenous infusion of nutrients and somatostatin in conscious dog. Regul Pept 1:265–271, 1981

    Google Scholar 

  20. Ormshee HS, Koehler SL, Telford GL: Somatostatin inhibits motilin-induced interdigestive contractile activity in the dog. Am J Dig Dis 23:781–788, 1978

    Google Scholar 

  21. Gullo L, Bolondi L, Scarpignato C, Priori P, Casanova P, Labó G: Effect of somatostatin and thyrotropin-releasing hormone on cholecystokinin-induced gallbladder emptying. Dig Dis Sci 31:1345–1350, 1986

    Google Scholar 

  22. Fisher RS, Rock E, Levin G, Malmud L: Effects of somatostatin on gallbladder emptying. Gastroenterology 92:885–890, 1987

    Google Scholar 

  23. Fiorucci S, Bosso R, Scionti L, DiSanto S, Annibale B, Delle Fave G, Morelli A: Neurohumoral control of gallbladder motility in healthy subjects and in diabetic patients with or without autonomic neuropathy. Dig Dis Sci 35:1089–1097, 1990

    Google Scholar 

  24. Dodds WJ, Groth WJ, Darweesh RMA, Lawson TL, Kisher SMA, Kern MK: Sonographyc measurement of gallbladder volume. Am J Radiol 145:1009–1011, 1985

    Google Scholar 

  25. Colton T: Statistics in Medicine. Boston, Little Brown and Company, 1976

    Google Scholar 

  26. Svenberg T, Cristofedes ND, Fitzpatrick ML, Areola-Ortiz F, Bloom SR, Welbourn RB: Interdigestive biliary output in man: Relationship to fluctuations in plasma motilin and effect of atropine. Gut 23:1024–1028, 1982

    Google Scholar 

  27. Chey WY, Lee KY, Tai HH: Endogenous plasma motilin concentration and the interdigestive myoelectric activity of the canine duodenum.In Gut Hormones. SR Bloom (ed). Edinburgh, Churchill-Livingstone, 1978, pp 355–358

    Google Scholar 

  28. Sarna SK, Chey WY, Condon RE, Dodds WJ, Myers T, Chang TM: Cause-and-effect relationship between motilin and migrating myoelectric complexes. Am J Physiol 245:G277-G284, 1983

    Google Scholar 

  29. Itoh Z, Mizumoto A, Ohtawa M, Ueki S, Sekiguchi T, Omura S: Motilide (erythromycin-523) mimics motilin in interdigestive gallbladder contraction in dogs and man. Gastroenterology 100:320, 1991 (abstract)

    Google Scholar 

  30. Sarna SK, Ryan RP, Brandon A: Erytromycin acts on presynaptic neurons to stimulate gastrointestinal motor activity. Gastroenterology 100:490, 1991, (abstract)

    Google Scholar 

  31. Matsumoto T, Sarna SK, Condon RE, Dodds WJ, Mochinaga N: Canine gallbladder cyclic motor activity. Am J Physiol 255:G409-G416, 1988

    Google Scholar 

  32. Rees WDW, Malagelada JR, Miller LJ, Go VLW: Human interdigestive and postprandial gastrointestinal motor and hormone pattern. Dig Dis Sci 27:321–329, 1982

    Google Scholar 

  33. Lee KY, Chang T, Chey WY: Effect of electrical stimulation of the vagus on plasma motilin concentration in dog. Life Sci 29:1093–1098, 1981

    Google Scholar 

  34. Reichlin SD: Somatostatin. N Engl J Med 309:1495–1501, 1983

    Google Scholar 

  35. Guillemin R: Somatostatin inhibits the release of acetylcholine induced electrically in the myenteric plexus. Endocrinology 99:1653–1654, 1976

    Google Scholar 

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Authors and Affiliations

  1. Istituto di Gastroenterologia ed Endoscopia Digestiva, Policlinico Monteluce, Università di Perugia, 06122, Perugia, Italy

    Stefano Fiorucci MD, Rachele Bosso MD & Antonio Morelli MD

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  1. Stefano Fiorucci MD
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  2. Rachele Bosso MD
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  3. Antonio Morelli MD
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Fiorucci, S., Bosso, R. & Morelli, A. Erythromycin stimulates gallbladder emptying and motilin release by atropine-sensitive pathways. Digest Dis Sci 37, 1678–1684 (1992). https://doi.org/10.1007/BF01299858

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  • DOI: https://doi.org/10.1007/BF01299858

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