Mechanism of Interdigestive Migrating Motor Complex

Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, Milwaukee, Wisconsin, USA.
Journal of neurogastroenterology and motility (Impact Factor: 2.3). 07/2012; 18(3):246-57. DOI: 10.5056/jnm.2012.18.3.246
Source: PubMed


Migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal contractions in the interdigestive state. This review article discussed the mechanism of gastrointestinal MMC. Luminal administration of 5-hydroxytryptamine (5-HT) initiates duodenal phase II followed by gastrointestinal phase III with a concomitant increase of plasma motilin release in conscious dogs. Duodenal 5-HT concentration is increased during gastric phase II and phase III. Intravenous infusion of motilin increases luminal 5-HT content and induces gastrointestinal phase III. 5-HT(4) antagonists significantly inhibits both of gastric and intestinal phase III, while 5-HT(3) antagonists inhibited only gastric phase III. These suggest that gastrointestinal MMC cycle is mediated via the interaction between motilin and 5-HT by the positive feedback mechanism. Gastric MMC is regulated via vagus, 5-HT(3/4) receptors and motilin, while intestinal MMC is regulated via intrinsic primary afferent neurons and 5-HT(4) receptors. Stress is highly associated with the pathogenesis of functional dyspepsia. Acoustic stress attenuates gastric phase III without affecting intestinal phase III in conscious dogs, via reduced vagal activity and increased sympathetic activity. It has been shown that subset of functional dyspepsia patients show reduced vagal activity and impaired gastric phase III. The physiological importance of gastric MMC is a mechanical and chemical cleansing of the empty stomach in preparation for the next meal. The impaired gastric MMC may aggravate dyspeptic symptoms following a food ingestion. Thus, maintaining gastric MMC in the interdigestive state is an important factor to prevent the postprandial dyspeptic symptoms.

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    • "5HT4 receptors are reportedly present in IPANs and in some other neuron types in the myenteric plexus [45]. Recently, Takahashi et al. [60] observed that 5HT4 receptors are important in regulating migrating motor complexes through IPANs. Taken together, these data indicate that a different stimulatory pathway exists between the motilin and the ghrelin effects and that IPANs may be implicated in the effects of ghrelin on GI motility. "
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    ABSTRACT: Here, we have reported that motilin can induce contractions in a dose-dependent manner in isolated Suncus murinus (house musk shrew) stomach. We have also shown that after pretreatment with a low dose of motilin (10(-10) M), ghrelin also induces gastric contractions at levels of 10(-10) M to 10(-7) M. However, the neural mechanism of ghrelin action in the stomach has not been fully revealed. In the present study, we studied the mechanism of ghrelin-induced contraction in vitro using a pharmacological method. The responses to ghrelin in the stomach were almost completely abolished by hexamethonium and were significantly suppressed by the administration of phentolamine, prazosin, ondansetron, and naloxone. Additionally, N-nitro-l-arginine methylester significantly potentiated the contractions. Importantly, the mucosa is essential for ghrelin-induced, but not motilin-induced, gastric contractions. To evaluate the involvement of intrinsic primary afferent neurons (IPANs), which are multiaxonal neurons that pass signals from the mucosa to the myenteric plexus, we examined the effect of the IPAN-related pathway on ghrelin-induced contractions and found that pretreatment with adenosine and tachykinergic receptor 3 antagonists (SR142801) significantly eliminated the contractions and GR113808 (5-hydroxytryptamine receptor 4 antagonist) almost completely eliminated it. The results indicate that ghrelin stimulates and modulates suncus gastric contractions through cholinergic, adrenergic, serotonergic, opioidergic neurons and nitric oxide synthases in the myenteric plexus. The mucosa is also important for ghrelin-induced gastric contractions, and IPANs may be the important interneurons that pass the signal from the mucosa to the myenteric plexus.
    Full-text · Article · Apr 2013 · PLoS ONE
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    • "The overall periodicity of the MMC in humans varies individually but is in the range of 80–120 min, with the active phase III lasting 15–25 min [95]. With meals the MMC is broken, and the work of the stomach starts to resemble a semi-active phase of the MMC until it empties completely [96]. After gastric emptying, the fasting MMC pattern is restored [97]. "
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    • "Obwodowe zakończenia nerwowe są umiejscowione w poszczególnych warstwach ściany przewodu pokarmowego: włókna współczulne w błonie surowiczej i mięśniowej , włókna przywspółczulne w obrębie błony śluzowej [33]. Wewnętrzne pierwotne neurony wstępujące (intrinsic primary afferent neurons -IPANs) przewodzą odruchy pod wpływem bodźców ze światła przewodu pokarmowego, takie jak wzrost ciśnienia, zmiana pH, obecność składników pokarmowych [66]. Receptory pobudzone przez swoiste czynniki wyzwalające uruchamiają drogi aferentne, które przekazują wrażenia: uczucie głodu , nudności czy rozciągania odbytnicy i pęcherza moczowego oraz przewodzą ból trzewny. "
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