Mechanism of interdigestive migrating motor complex

Abstract

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.

Keywords: Autonomic pathways; Enterochromaffin cell; Motilin; Serotonin.

Figure 1

Suggested mechanism of motilin-induced gastric migrating motor complex by Dr. Itoh. Released motilin from the duodenal mucosa reaches at the area postrema and activates 5-hydroxytryptamine (5-HT) neurons at the dorsal vagal complex. Stimulation of 5-HT neurons activates vagal efferents through 5-HT₃ receptors. DVC, dorsal vagal complex; ACh, acetylcholine; MMC, migrating motor complex.

Figure 2

Luminal concentration of 5-hydroxytryptamine (5-HT) of the duodenum during migrating motor complex cycle. During duodenal phase I, the luminal concentration of 5-HT of the duodenum is 29 ng/mL, which is significantly increased to 59 ng/mL during the duodenal phase II. Luminal concentration of 5-HT of the duodenum is further increased to 250 ng/mL during phase III. In contrast to the duodenum, luminal concentration of 5-HT of the stomach is not significantly changed during phase I, II and III. Open squares indicate phase II contractions and closed squares indicate phase III contractions. Adapted from Nakajima et al.

Figure 3

Simultaneous recording of gastrointestinal migrating motor complex and duodenal pressure. During phase I, duodenal pressure changes are observed. Luminal pressure of the duodenum increases by 20-30 H₂O, just before the occurrence of duodenal phase II and III (an open arrow). Duodenal phase II (an open arrow) is followed by gastric phase III (a solid arrow). Open squares indicate phase II contractions and closed squares indicate phase III contractions. Adapted from Nakajima et al.

Figure 4

Possible mechanism of gastrointestinal migrating motor complex during gastric phase I (A), phase II (B) and phase III (C). During gastic phase I, the basal secretion of gastric, pancreatic and biliary juices gradually increases the luminal pressure of the duodenum (A), resulting in 5-hydroxytryptamine (5-HT) release from enterochromaffin cells. Released 5-HT initiates duodenal phase II via 5-HT₄ receptors of intrinsic primary afferent neurons (IPAN) (A). Duodenal phase II causes further increase of duodenal pressure, which stimulates more 5-HT release. This positive circuit (pressure increase and 5-HT release) gradually enhances the amplitude of duodenal phase II, leading to duodenal phase III. Finally, maximally increased duodenal pressure stimulates motilin release (B). Released motilin stimulates large amounts of 5-HT release which acts on 5-HT₃ receptors of vagal afferent, in addition to 5-HT₄ receptors of IPAN. Released motilin induces gastric phase III via vago-vagal reflex (C). Black dots indicate 5-HT granules/particles. Open triangle indicates 5-HT₄ receptors and open circle indicates 5-HT₃ receptors. ACh, acetylcholine; EC cell, enterochromaffin cell.

Figure 5

Possible mechanism of gastric migrating motor complex. Released motilin from the duodenal mucosa stimulates the release of 5-hydroxytryptamine (5-HT) from the duodenal enterochromaffin cells. Released 5-HT activates 5-HT₃ receptors of the vagal afferent. The sensory information is carried to the brain stem (nucleus tractus solitarius and dorsal motor nucleus of the vagus) and activates vagal efferent. Finally, motilin initiates gastric phase III via vago-vagal reflex. DMV, dorsal motor nucleus of the vagus; NTS, nucleus tractus solitarius; ACh, acetylcholine; MMC, migrating motor complex.

Figure 6

Effects of acoustic stress on gastrointestinal migrating motor complex (MMC) (A) and heart rate viability (B) in conscious dogs. Acoustic stress almost completely abolishes gastric MMC (body and antrum) without affecting intestinal MMC (duodenum). During acoustic stress loading, heart rate and sympathetic tone (low frequency component; LF) are increased, while parasympathetic tone (high frequency component; HF) is reduced. As a result, the ratio between sympathetic tone and parasympathetic tone (LF/HF) is increaed by acoustic stress. Adapted from Taniguchi et al.