Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.576
Peer-review started: October 27, 2020
First decision: December 13, 2020
Revised: December 24, 2020
Accepted: January 13, 2021
Article in press: January 13, 2021
Published online: February 21, 2021
Interdigestive migrating motor complexes (MMC) produce periodic contractions in the gastrointestinal tract, but the exact mechanism of action still remains unclear. Intramuscular interstitial cells of Cajal (ICC-IM) participate in gastrointestinal hormone and neuromodulation, but the correlation between ICC-IM and MMC is also unclear. We found that xiangbinfang granules (XBF) mediated the phase III contraction of MMC. Here, the effects of XBF on gastric antrum motility in W/Wv mice and the effects of ICC-IM on gastric antrum MMC are reported.
To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum motility.
The density of c-kit-positive ICC myenteric plexus (ICC-MP) and ICC-IM in the antral muscularis of W/Wv and wild-type (WT) mice was examined by confocal microscopy. The effects of XBF on gastric antrum slow waves in W/Wv and WT mice were recorded by intracellular amplification recording. Micro-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/Wv and WT mice.
In the gastric antrum of W/Wv mice, c-kit immunoreactivity was significantly reduced, and no ICC-IM network was observed. Spontaneous rhythmic slow waves also appeared in the antrum of W/Wv mice, but the amplitude of the antrum slow wave decreased significantly in W/Wv mice (22.62 ± 2.23 mV vs 2.92 ± 0.52 mV, P < 0.0001). MMCs were found in 7 of the 8 WT mice but no complete MMC cycle was found in W/Wv mice. The contractile frequency and amplitude index of the gastric antrum were significantly increased in conscious WT compared to W/Wv mice (frequency, 3.53 ± 0.18 cpm vs 1.28 ± 0.12 cpm; amplitude index, 23014.26 ± 1798.65 mV·20 min vs 3782.16 ± 407.13 mV·20 min; P < 0.0001). XBF depolarized smooth muscle cells of the gastric antrum in WT and W/Wv mice in a dose-dependent manner. Similarly, the gastric antrum motility in WT mice was significantly increased after treatment with XBF 5 mg (P < 0.05). Atropine (0.1 mg/kg) blocked the enhancement of XBF in WT and W/Wv mice completely, while tetrodotoxin (0.05 mg/kg) partially inhibited the enhancement by XBF.
ICC-IM participates in the regulation of gastric antrum MMC in mice. XBF induces MMC III-like contractions that enhance gastric antrum motility via ICC-IM in mice.
Core Tip: This study shows that intramuscular interstitial cells of Cajal (ICC-IM) play crucial roles in regulating the activity of gastric antral migrating motor complexes (MMC). This may be an important bridge between the vagus, enteric nervous system and motilin to regulate smooth muscle contraction. Through the muscarinic receptor pathway on ICC-IM, the Chinese medicine Xiangbinfang granules depolarize smooth muscle cells and initiates an action potential, changing the periodic motion of MMC into a phase III-like contraction pattern in the gastric antrum of mice.