Abstract
Background
The migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal contractions in the interdigestive state. This study was designed to clarify the mechanisms of gastric MMC (G-MMC) and intestinal MMC (I-MMC) in conscious dogs.
Methods
Five strain gauge transducers were implanted on the stomach and intestine. To investigate the correlation between luminal 5-HT and phase III contractions, gastric and duodenal juices were collected during the MMC cycle. The 5-HT concentrations in gastric and duodenal juice were measured by HPLC. To investigate whether luminal 5-HT initiates MMC, 5-HT (10−8–10−6 M, 10 ml) was administered into the duodenum 20 min after gastric phase III. To investigate the involvement of 5-HT3 or 5-HT4 receptors in mediating G-MMC and I-MMC, 5-HT3 antagonists (ondansetron) or 5-HT4 antagonists (GR 125,487) were infused for 120 min.
Results
Luminal administration of 5-HT (10−6 M) initiated duodenal phase II followed by G-MMC and I-MMC with a concomitant increased release of plasma motilin. The duodenal 5-HT concentration was significantly increased during phase II (59 ± 9 ng/ml) and phase III (251 ± 21 ng/ml) compared to that of phase I (29 ± 5 ng/ml). On the other hand, the 5-HT content in the stomach was not significantly changed throughout the MMC cycle. Intravenous infusion of motilin (0.3 μg/kg/h) increased the luminal 5-HT content and induced G-MMC and I-MMC. 5-HT4 antagonists significantly inhibited both G-MMC and I-MMC, while 5-HT3 antagonists inhibited only G-MMC.
Conclusion
It is suggested that the MMC cycle is mediated by a positive feedback mechanism via the interaction between motilin and 5-HT.
Similar content being viewed by others
Abbreviations
- EC cell:
-
Enterochromaffin cell
- HPLC:
-
High-performance liquid chromatography
- IPAN:
-
Intrinsic primary afferent neurons
- MMC:
-
Migrating motor complex
- MI:
-
Motility index
- RIA:
-
Radioimmunoassay
References
Vantrappen G, Janssens J, Hellemans J, Ghoos Y. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest. 1977;59:1158–66.
Itoh Z, Takeuchi S, Aizawa I, Mori K, Taminato T, Seino Y, et al. Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs. Am J Dig Dis. 1978;23:929–35.
Vantrappen G, Janssens J, Peeters TL, Bloom SR, Christofides ND, Hellemans J. Motilin and the interdigestive migrating motor complex in man. Dig Dis Sci. 1979;24:497–500.
Mochiki E, Satoh M, Tamura T, Haga N, Suzuki H, Mizumoto A, et al. Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog. Gastroenterology. 1996;111:1456–64.
Sarna S, Chey WY, Condon RE, Dodds WJ, Myers T, Chang TM. Cause-and-effect relationship between motilin and migrating myoelectric complexes. Am J Physiol. 1983;245:G277–84.
Poitras P, Steinbach JH, VanDeventer G, Code CF, Walsh JH. Motilin-independent ectopic fronts of the interdigestive myoelectric complex in dogs. Am J Physiol. 1980;239:G215–20.
Lee KY, Chang TM, Chey WY. Effect of rabbit antimotilin serum on myoelectric activity and plasma motilin concentration in fasting dog. Am J Physiol. 1983;245:G547–53.
Suzuki H, Mochiki E, Haga N, Shimura T, Itoh Z, Kuwano H. Effect of duodenectomy on gastric motility and gastric hormones in dogs. Ann Surg. 2001;233:353–9.
Hall KE, Greenberg GR, El-Sharkawy TY, Diamant NE. Vagal control of migrating motor complex-related peaks in canine plasma motilin, pancreatic polypeptide, and gastrin. Can J Physiol Pharmacol. 1983;61:1289–98.
Chung SA, Valdez DT, Diamant NE. Adrenergic blockage does not restore the canine gastric migrating motor complex during vagal blockade. Gastroenterology. 1992;103:1491–7.
Tanaka T, Kendrick ML, Zyromski NJ, Meile T, Sarr MG. Vagal innervation modulates motor pattern but not initiation of canine gastric migrating motor complex. Am J Physiol Gastrointest Liver Physiol. 2001;281:G283–92.
Ormsbee HS 3rd, Silber DA, Hardy FE Jr. Serotonin regulation of the canine migrating motor complex. J Pharmacol Exp Ther. 1984;231:436–40.
Gorard DA, Libby GW, Farthing MJ. 5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake. Gut. 1994;35:496–500.
Yoshida N, Mizumoto A, Iwanaga Y, Itoh Z. Effects of 5-hydroxytryptamine 3 receptor antagonists on gastrointestinal motor activity in conscious dogs. J Pharmacol Exp Ther. 1991;256:272–8.
Wilmer A, Tack J, Coremans G, Janssens J, Peeters T, Vantrappen G. 5-Hydroxytryptamine-3 receptors are involved in the initiation of gastric phase-3 motor activity in humans. Gastroenterology. 1993;105:773–80.
Ueno T, Uemura K, Harris MB, Pappas TN, Takahashi T. Role of vagus nerve in postprandial antropyloric coordination in conscious dogs. Am J Physiol Gastrointest Liver Physiol. 2005;288:G487–95.
Foxx-Orenstein AE, Kuemmerle JF, Grider JR. Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Gastroenterology. 1996;111:1281–90.
Gershon MD. Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. J Clin Gastroenterol. 2005;39:S184–93.
Ahlman H, DeMagistris L, Zinner M, Jaffe BM. Release of immunoreactive serotonin into the lumen of the feline gut in response to vagal nerve stimulation. Science. 1981;213:1254–5.
Gronstad K, Dahlstrom A, Florence L, Zinner MJ, Ahlman J, Jaffe BM. Regulatory mechanisms in endoluminal release of serotonin and substance P from feline jejunum. Dig Dis Sci. 1987;32:393–400.
Kellum J, McCabe M, Schneier J, Donowitz M. Neural control of acid-induced serotonin release from rabbit duodenum. Am J Physiol. 1983;245:G824–31.
Ferrara A, Zinner MJ, Jaffe BM. Intraluminal release of serotonin, substance P, and gastrin in the canine small intestine. Dig Dis Sci. 1987;32:289–94.
Fujimiya M, Okumiya K, Kuwahara A. Immunoelectron microscopic study of the luminal release of serotonin from rat enterochromaffin cells induced by high intraluminal pressure. Histochem Cell Biol. 1997;108:105–13.
Cooke HJ, Montakhab M, Wade PR, Wood JD. Transmural fluxes of 5-hydroxytryptamine in guinea pig ileum. Am J Physiol. 1983;244:G421–5.
Martel F, Monteiro R, Lemos C, Vieira-Coelho MA. In vitro and in vivo effect of fluoxetine on the permeability of 3H-serotonin across rat intestine. Can J Physiol Pharmacol. 2004;82:940–50.
Fukumoto S, Tatewaki M, Yamada T, Fujimiya M, Mantyh C, Voss M, et al. Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1269–76.
Tanaka T, Mizumoto A, Mochiki E, Haga N, Suzuki H, Itoh Z. Relationship between intraduodenal 5-hydroxytryptamine release and interdigestive contractions in dogs. J Smooth Muscle Res. 2004;40:75–84.
Kellum JM, Maxwell RJ, Potter J, Kummerle JF. Motilin’s induction of phasic contractility in canine jejunum is mediated by the luminal release of serotonin. Surgery. 1986;100:445–53.
Tougas G, Allescher HD, Dent J, Daniel EE. Sensory nerves of the intestines: role in control of pyloric region of dogs. Adv Exp Med Biol. 1991;298:199–211.
Itoh Z. Motilin and clinical application. Peptides. 1997;18:593–608.
Glatzle J, Sternini C, Robin C, Zittel TT, Wong H, Reeve JR Jr, et al. Expression of 5-HT3 receptors in the rat gastrointestinal tract. Gastroenterology. 2002;123:217–26.
Grider JR, Kuemmerle JF, Jin JG. 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons. Am J Physiol. 1996;270:G778–82.
Grider JR, Foxx-Orenstein AE, Jin JG. 5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine. Gastroenterology. 1998;115:370–80.
DiMagno EP, Hendricks JC, Go VL, Dozois RR. Relationships among canine fasting pancreatic and biliary secretions, pancreatic duct pressure, and duodenal phase III motor activity—Boldyreff revisited. Dig Dis Sci. 1979;24:689–93.
Quigley EM, Donovan JP, Lane MJ, Gallagher TF. Antroduodenal manometry. Usefulness and limitations as an outpatient study. Dig Dis Sci. 1992;37:20–8.
Kusano M, Sekiguchi T, Kawamura O, Kikuchi K, Miyazaki M, Tsunoda T, et al. Further classification of dysmotility-like dyspepsia by interdigestive gastroduodenal manometry and plasma motilin level. Am J Gastroenterol. 1997;92:481–4.
Holtmann G, Goebell H, Jockenhoevel F, Talley NJ. Altered vagal and intestinal mechanosensory function in chronic unexplained dyspepsia. Gut. 1998;42:501–6.
Acknowledgment
The authors are thankful to Dr. Zen Itoh (Prof. Emeritus, Gunma University, Japan) for his valuable advice during the study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nakajima, H., Mochiki, E., Zietlow, A. et al. Mechanism of interdigestive migrating motor complex in conscious dogs. J Gastroenterol 45, 506–514 (2010). https://doi.org/10.1007/s00535-009-0190-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-009-0190-z