Published online Nov 28, 2018. doi: 10.3748/wjg.v24.i44.4989
Peer-review started: August 24, 2018
First decision: October 5, 2018
Revised: November 7, 2018
Accepted: November 7, 2018
Article in press: November 7, 2018
Published online: November 28, 2018
To investigate the distribution and function of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in the proximal and distal colon.
The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes (CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation (EFS)-induced inhibitory junction potentials (IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.
Treatment with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulation-induced nitric oxide (NO)/ICC-dependent slow IJPs (sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulation-induced purinergic/PDGFRα-dependent fast IJPs (fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1 (ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3 (SK3) in the distal colon were much higher.
The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.
Core tip: The different distributions of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in the different parts of the colon result in a pressure gradient in the colon that propels the feces to the anus. Nitric oxide (NO) is mainly involved in the regulation of contraction through ICCs, and purine mainly participates in relaxation through PDGFRα+ cells. The regulation of the inhibitory transmitter NO and purine through the two kinds of interstitial cells (ICCs and PDGFRα+ cells) is very important for rhythmic colonic migrating motor complexes, which are the main driving force underlying colon transit.