Abstract

The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are located in the same area as the myenteric plexus. ICC-MP networks are linked to the generation of electrical pacemaker activity that causes spontaneous gastrointestinal (GI) contractions; however, its role in GI transit is not clear. The aim of this study was to comprehensively investigate the effect of ICC-MP disruption on GI transit in vivo using W/W v mice, partially ICC-deficient model mice. In this study, we measured GI transit using a 13C-octanoic acid breath test, an orally administered dye and a bead expulsion assay. ICC were detected by immunohistochemical staining for c-Kit, a specific marker for ICC. Interestingly, we found that gastric emptying in W/W v mice was normal. We also found that the ability of small intestinal and colonic transit was significantly reduced in W/W v mice. Immunohistochemical staining using whole-mount muscularis samples revealed that c-Kit-positive ICC-MP networks were formed in wild-type mice. In contrast, ICC-MP networks in W/W v mice were maintained only in the gastric antrum and were significantly reduced in the ileum and colon. No significant changes were observed in the nerve structures of the myenteric plexus in W/W v mice. These findings suggest that ICC-MP contribute to GI transit as a powerful driving function in vivo.

Highlights

  • Gastrointestinal (GI) transit is a complex process that integrates contraction, relaxation, and transit (Sanders et al, 2012)

  • Several reports showed that when ACK2, a monoclonal antibody that inhibits the function of the c-Kit receptor, was administered to mice starting immediately after birth, spontaneous contraction of the small intestine was reduced with the disappearance of interstitial cells of Cajal (ICC)-MP and slow waves (Sato et al, 1996; Torihashi et al, 1995). These findings suggest that the slow waves produced by ICC-MP raise the membrane potential of smooth muscle cells (SMC) above the threshold of the smooth muscle action potential, which results in spontaneous contraction of SMC and contributes to the spontaneous movement of the GI tract

  • As a result of the measurement, there was no significant difference between WT mice and W/Wv mice in all parameters (Figure 1B)

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Summary

Introduction

Gastrointestinal (GI) transit is a complex process that integrates contraction, relaxation, and transit (Sanders et al, 2012). These integrative processes are in vivo functions responsible for the digestion and absorption of food as well as normal GI motility functions that maintain health in humans and animals. In addition to these cell groups, it was determined that interstitial cells of Cajal (ICC) produce a complicated locomotor pattern of the GI tract that is attracting attention from the clinical standpoint (Blair et al, 2014; Iino et al, 2006; Sanders et al, 2014a). The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) form cellular networks.

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