scholarly journals Interstitial cells of Cajal and human colon motility in health and disease

2021 ◽  
Author(s):  
Jan D. Huizinga ◽  
Amer Hussain ◽  
Ji-Hong Chen
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Colonic Motility ◽  
Human Colon ◽  
Interstitial Cells ◽  
Motor Dysfunction ◽  
Slow Transit Constipation ◽  
Motor Patterns ◽  
Colonic Motor ◽  
Cells Of Cajal

Our understanding of human colonic motility, and autonomic reflexes that generate motor patterns, has increased markedly through high-resolution manometry. Details of the motor patterns are emerging related to frequency and propagation characteristics that allow linkage to interstitial cells of Cajal (ICC) networks. In studies on colonic motor dysfunction requiring surgery, ICC are almost always abnormal or significantly reduced. However, there are still gaps in our knowledge about the role of ICC in the control of colonic motility and there is little understanding of a mechanistic link between ICC abnormalities and colonic motor dysfunction. This review will outline the various ICC networks in the human colon and their proven and likely associations with the enteric and extrinsic autonomic nervous systems. Based on our extensive knowledge of the role of ICC in the control of gastrointestinal motility of animal models and the human stomach and small intestine, we propose how ICC networks are underlying the motor patterns of the human colon. The role of ICC will be reviewed in the autonomic neural reflexes that evoke essential motor patterns for transit and defecation. Mechanisms underlying ICC injury, maintenance, and repair will be discussed. Hypotheses are formulated as to how ICC dysfunction can lead to motor abnormalities in slow transit constipation, chronic idiopathic pseudo-obstruction, Hirschsprung's disease, fecal incontinence, diverticular disease, and inflammatory conditions. Recent studies on ICC repair after injury hold promise for future therapies.

scholarly journals Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal

2017 ◽  
Vol 313 (5) ◽  
pp. G419-G433 ◽  
Author(s):  
Leonie Durnin ◽  
Andrea Lees ◽  
Sheerien Manzoor ◽  
Kent C. Sasse ◽  
Kenton M. Sanders ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Interstitial Cells Of Cajal ◽  
Colonic Motility ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Interstitial Cells ◽  
Partial Loss ◽  
Purinergic Neurotransmission ◽  
Cells Of Cajal

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα+) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in KitW/KitW-v ( W/Wv) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD+)/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5′-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/Wv, Nos1−/−, and Prkg1−/− mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/Wv mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/Wv mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric oxide (NO) and intramuscular interstitial cells of Cajal (ICC-IM) in modulating neural release of purines in colon. We found that NO inhibited release of purines in human, monkey, and murine colons and that colons from KitW/KitW-v ( W/Wv) mice, which present with partial loss of ICC-IM, demonstrated augmented neural release of purines. Interactions between nitrergic and purinergic neurotransmission may affect motility in disease conditions with ICC-IM deficiencies.

scholarly journals Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide-Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Shuai Yan ◽  
Yin-zi Yue ◽  
Xiao-peng Wang ◽  
Hong-li Dong ◽  
Shu-guang Zhen ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Colonic Motility ◽  
Functional Constipation ◽  
Serum Levels ◽  
Interstitial Cells ◽  
Slow Transit Constipation ◽  
Mrna Levels ◽  
Aqueous Extracts ◽  
Slow Transit ◽  
Cells Of Cajal

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.

Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal

1984 ◽  
Vol 246 (3) ◽  
pp. G305-G315 ◽  
Author(s):  
E. E. Daniel ◽  
V. Posey-Daniel
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Complete Relaxation ◽  
Granular Vesicles ◽  
Cells Of Cajal

The structures of the lower esophageal sphincter (LES) and body circular muscle (BCM) from opossum were compared as to neural and muscular structures and the structural relations of interstitial cells of Cajal to nerves and muscle cells. Both LES and BCM were densely innervated by nerves with varicosities containing many small agranular vesicles and a few large granular vesicles. These nerves were more closely related structurally to the interstitial cells of Cajal than to smooth muscle cells. More gap junctions were observed between smooth muscle cells and between interstitial cells of Cajal and smooth muscle cells in BCM than in LES. Those between smooth muscle cells were larger in BCM. Complete relaxation of the LES strip by isoproterenol reduced these differences but did not eliminate them. The finding that interstitial cells of Cajal often had gap-junction contacts to smooth muscle and close associations with nerves is consistent with the hypothesis that interstitial cells are intercalated between the nerves and muscles and may mediate nerve responses. These findings also suggest that LES muscle cells may be less well coupled electrically than BCM muscle cells.

Role of Interstitial Cells of Cajal in Motility Disorders of the Bowel

2003 ◽  
Vol 98 (3) ◽  
pp. 618-624 ◽  
Author(s):  
Dhanpat Jain ◽  
Khalid Moussa ◽  
Manish Tandon ◽  
Joan Culpepper-Morgan ◽  
Deborah D. Proctor
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Motility Disorders ◽  
Cells Of Cajal

scholarly journals Effects of gap junction inhibition on contraction waves in the murine small intestine in relation to coupled oscillator theory

2015 ◽  
Vol 308 (4) ◽  
pp. G287-G297 ◽  
Author(s):  
Sean P. Parsons ◽  
Jan D. Huizinga
Keyword(s):  
Small Intestine ◽  
Gap Junction ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Coupled Oscillator ◽  
Motor Patterns ◽  
Mapping System ◽  
Murine Small Intestine ◽  
Cells Of Cajal ◽  
Oscillator Theory

Waves of contraction in the small intestine correlate with slow waves generated by the myenteric network of interstitial cells of Cajal. Coupled oscillator theory has been used to explain steplike gradients in the frequency (frequency plateaux) of contraction waves along the length of the small intestine. Inhibition of gap junction coupling between oscillators should lead to predictable effects on these plateaux and the wave dislocation (wave drop) phenomena associated with their boundaries. It is these predictions that we wished to test. We used a novel multicamera diameter-mapping system to measure contraction along 25- to 30-cm lengths of murine small intestine. There were typically two to three plateaux per length of intestine. Dislocations could be limited to the wavefronts immediately about the terminated wave, giving the appearance of a three-pronged fork, i.e., a fork dislocation; additionally, localized decreases in velocity developed across a number of wavefronts, ending with the terminated wave, which could appear as a fork, i.e., slip dislocations. The gap junction inhibitor carbenoxolone increased the number of plateaux and dislocations and decreased contraction wave velocity. In some cases, the usual frequency gradient was reversed, with a plateau at a higher frequency than its proximal neighbor; thus fork dislocations were inverted, and the direction of propagation was reversed. Heptanol had no effect on the frequency or velocity of contractions but did reduce their amplitude. To understand intestinal motor patterns, the pacemaker network of the interstitial cells of Cajal is best evaluated as a system of coupled oscillators.

scholarly journals The presence and role of interstitial cells of Cajal in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius)

2016 ◽  
Vol 220 (3) ◽  
pp. 347-357 ◽  
Author(s):  
Jeroen Brijs ◽  
Grant W. Hennig ◽  
Anna-Maria Kellermann ◽  
Michael Axelsson ◽  
Catharina Olsson
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Shorthorn Sculpin ◽  
Myoxocephalus Scorpius ◽  
Proximal Intestine ◽  
Cells Of Cajal
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