scholarly journals A close relationship between networks of interstitial cells of Cajal and gastrointestinal transit in vivo

Author(s):  
Kamizaki Moe ◽  
Kazuhisa Kishi ◽  
Noriyuki Kaji ◽  
Satoshi Iino ◽  
Masatoshi Hori
2020 ◽  
Vol 11 ◽  
Author(s):  
Kazuhisa Kishi ◽  
Moe Kamizaki ◽  
Noriyuki Kaji ◽  
Satoshi Iino ◽  
Masatoshi Hori

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/Wv 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/Wv mice was normal. We also found that the ability of small intestinal and colonic transit was significantly reduced in W/Wv 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/Wv 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/Wv mice. These findings suggest that ICC-MP contribute to GI transit as a powerful driving function in vivo.


2017 ◽  
Vol 43 (5) ◽  
pp. 1790-1802 ◽  
Author(s):  
Hyun Jung Kim ◽  
Taewon Han ◽  
Yun Tai Kim ◽  
Insuk So ◽  
Byung Joo Kim

Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.


2000 ◽  
Vol 118 (4) ◽  
pp. A634
Author(s):  
Christophe Porcher ◽  
Monique Henry ◽  
Benoit La Roche ◽  
Marie-Odile Christen ◽  
Yvon Jule

2005 ◽  
Vol 289 (2) ◽  
pp. G291-G299 ◽  
Author(s):  
Akiko Terauchi ◽  
Daisuke Kobayashi ◽  
Hiroshi Mashimo

Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c-Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient (nNOS−/−), eNOS-deficient (eNOS−/−), and W/Wv mice (lacking certain c-Kit-expressing ICC) with or without l-arginine or Nω-nitro-l-arginine methyl ester (l-NAME) treatment. Moreover, the basal tone and response to electrical field stimulation (EFS) were studied in organ bath using wild-type and mutant IAS. In vivo, the basal tone of eNOS−/− was higher and W/Wv was lower than wild-type and nNOS−/− mice. l-Arginine administered rectally, but not intravenously, decreased the basal tone in wild-type, nNOS−/−, and W/Wv mice. However, neither l-arginine nor l-NAME affected basal tone in eNOS−/− mice. In vitro, l-arginine decreased basal tone in wild-type and nNOS−/− IAS but not in eNOS−/− or wild-type IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS−/−, and W/Wv mice but absent in all nNOS−/− mice. EFS-induced IAS relaxation was also reduced in nNOS−/− IAS. Thus the basal IAS tone is largely controlled by eNOS in the mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be essential for the RAIR.


2015 ◽  
Vol 148 (4) ◽  
pp. S-79
Author(s):  
Sabriya A. Syed ◽  
Gabriella B. Gajdos ◽  
Srdjan Milosavljevic ◽  
Yujiro Hayashi ◽  
Raul A. Urrutia Sabine Klein ◽  
...  

2018 ◽  
Author(s):  
Sabriya A. Syed ◽  
Yujiro Hayashi ◽  
Jeong-Heon Lee ◽  
Huihuang Yan ◽  
Andrea Lorincz ◽  
...  

SUMMARYPhysiological interconversion between specialized cell types has only been described in a few mammalian tissues and the mechanisms remain obscure. Using genetic lineage tracing during postnatal development and in-vitro models we demonstrate conversion of gastric interstitial cells of Cajal (ICC), regulatory cells that electrically pace phasic contractions and mediate nitrergic and cholinergic neural control of smooth muscle cells, into phenotypically distinct “fibroblast-like” interstitial cells (FLC), which only mediate purinergic signaling. Mechanistically, we find this transition to be epigenetically governed by H3K27 trimethylation of cell identity-related promoters whose susceptibility to repression is predicted by H3K27 acetylation patterns in ICC. The phenotypic switch was reversible by inhibition, knockdown or in-vivo genomic inactivation of the polycomb H3K27 methyl-transferase Ezh2. These results demonstrate a role for Ezh2-mediated epigenetic repression in physiological mammalian transdifferentiation and identify FLC as a reserve from which ICC can potentially be restored in common gastrointestinal disorders where ICC are depleted.GRAPHICAL ABSTRACTHIGHLIGHTSGastric pacemaker cells (ICC) transdifferentiate into quiescent cells (FLC) in vivoICC-to-FLC shift switches neural control from nitrergic/cholinergic to purinergicEzh2-mediated H3K27me3 represses cell-identity genes during ICC-to-FLC transitionEzh2 inhibition restores ICC numbers, phenotype and functioneTOC BLURBSyed et al. find aging to cause transdifferentiation of gastric pacemaker cells (interstitial cells of Cajal, ICC), which also communicate cholinergic and nitrergic neurotransmission to smooth muscle cells, into quiescent “fibroblast-like cells” (FLC), which only mediate purinergic signals. This switch is governed by Ezh2, whose inhibition can reverse ICC depletion.


2005 ◽  
Vol 289 (3) ◽  
pp. G539-G549 ◽  
Author(s):  
Xuan-Yu Wang ◽  
Wim J. E. P. Lammers ◽  
Premysl Bercik ◽  
Jan D. Huizinga

The frequency and propagation velocity of distension-induced peristaltic contractions in the antrum and duodenum are distinctly different and depend on activation of intrinsic excitatory motoneurons as well as pacemaker cells, the interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because ICC are critical for coordination of motor activities along the long axis of many regions in the gut, the role of ICC in antroduodenal coordination was investigated. We used immunohistochemistry, electron microscopy, simultaneous multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and rats. A strongly reduced number of ICC-AP with loss of network characteristics was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3 mm in mice. Between antrum and duodenum, there was no interaction of electrical activities and in the absence of gastric emptying, there was no coordination of motor activities. When the pyloric sphincter opened, 2.4 s before the front of the antral wave reached the pylorus, the duodenum distended after receiving gastric content and aboral duodenal peristalsis was initiated, often disrupting other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric region allows the antrum and duodenum to have distinct uncoordinated motor activities. Coordination of aborally propagating peristaltic antral and duodenal activity is initiated by opening of the pylorus, which is followed by distention-induced duodenal peristalsis. Throughout this coordinated motor activity, the pacemaker systems in antrum and duodenum remain independent.


2001 ◽  
Vol 120 (5) ◽  
pp. A201-A201 ◽  
Author(s):  
P STREGE ◽  
A RICH ◽  
Y OU ◽  
S GIBBONS ◽  
M SARR ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document