Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters

Ward, Sean M.; Morris, G. M.; Reese, Lee; Wang, Xuan-Yu; Sanders, Kenton M.

doi:10.1016/s0016-5085(98)70198-2

Cited by 266 publications

(365 citation statements)

References 28 publications

Supporting

Mentioning

334

Contrasting

Unclassified

Order By: Relevance

“…The observation that tissues of W/W v animals retain responsiveness to exogenous ACh contrast with the effects of losing IC-IM on NO-dependent inhibitory responses (Burns et al, 1996;Ward et al, 1998). In those studies, tissues of W/W v animals lost electrical responsiveness to exogenous NO, suggesting that IC-IM express critical transduction mechanisms or ionic conductances that mediate postjunctional inhibitory responses.…”

Section: Discussionmentioning

confidence: 96%

“…Blockade of Kit receptors (Torihashi et al, 1995(Torihashi et al, , 1999Ward et al, 1997;Ordog et al, 1999) and use of c-kit mutant animals (Ward et al, 1994;Huizinga et al, 1995;Burns et al, 1996) have proven to be valuable experimental manipulations to determine the physiological role of ICC. For example, animals that lack intramuscular ICC have profoundly reduced enteric inhibitory responses, supporting a role for ICC in neurotransmission (Burns et al, 1996;Ward et al, 1998).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons

et al. 2000

Self Cite

View full text Add to dashboard Cite

Interstitial cells of Cajal (ICC) are interposed between enteric neurons and smooth muscle cells in gastrointestinal muscles. The role of intramuscular ICC (IC-IM) in mediating enteric excitatory neural inputs was studied using gastric fundus muscles of wild-type animals and W/W v mutant mice, which lack IC-IM. Excitatory motor neurons, labeled with antibodies to vesicular acetylcholine transporter or substance-P, were closely associated with IC-IM. Immunocytochemistry showed close contacts between enteric neurons and IC-IM. IC-IM also formed gap junctions with smooth muscle cells. Electrical field stimulation yielded fast excitatory junction potentials in the smooth muscle that were blocked by atropine. Neural responses were greatly reduced in muscles of W/W v animals. Loss of cholinergic responses in W/W v muscles seemed to be caused by the loss of close synaptic contacts between motor neurons and IC-IM, because these muscles were not less responsive to exogenous acetylcholine than were wild-type muscles. W/W v muscles also responded to excitatory nerve stimulation when the breakdown of acetylcholine was blocked by neostigmine. The density of cholinergic nerve bundles within the muscles was not significantly different in wild-type and W/W v muscles, and similar amounts of 14 [C]choline were released from preloaded wildtype and W/W v muscles in response to nerve stimulation. The impact of losing IC-IM on gastric compliance was also evaluated in intact stomachs. Pressure increased as a function of fluid volume and infusion rate in wild-type animals, but W/W v animals showed little basal tone and minimal increases in pressure with fluid infusions. These data suggest that IC-IM play a major role in receiving cholinergic excitatory inputs from the enteric nervous system in the murine fundus.

show abstract

Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons

et al. 2000

Self Cite

View full text Add to dashboard Cite

show abstract

“…ICC-MY were also suggested to be important for inducing slow waves in the gastric antrum (Burns et al, 1996). In contrast, ICC-IM were suggested to be important for i.j.ps and relaxation in the lower esophageal sphincter (Ward et al, 1998), gastric fundus (Burns et al, 1996;Beckett et al, 2002) and pyloric sphincter (Ward et al, 1998). The importance of ICC-IM in e.j.ps and contraction was also reported in the gastric fundus (Ward et al, 2000;Beckett et al, 2002).…”

Section: Discussionmentioning

confidence: 96%

“…However, there are few studies on its role in the motility of the gastrointestinal tract. A limited number of reports by studying the mechanical responses induced by EFS argued its role in motility (Maeda et al, 1992;Burns el al., 1996;Ward et al, 1998;Ward et al, 2000;Beckett et al, 2002). Most notably the role of ICC in peristaltic movements has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

Okishio

Takeuchi

Fujita

et al. 2005

J. Smooth Muscle Res.

View full text Add to dashboard Cite

Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W V mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.

show abstract

“…Laboratory Investigation • March 2001 • Volume 81 • Number 3 Maeda et al, 1992;Torihashi et al, 1995;Ward et al, 1998;Yamataka et al, 1998), we examined c-kit expression in the distal colon of HGF/SF transgenic mice by Northern blot analysis. The level of c-kit expression in the transgenic colon was essentially equal to that in wild-type mice (Fig.…”

Section: Intestinal Dysfunction In Hgf/sf Transgenic Micementioning

confidence: 99%

Ulcerative Proctitis, Rectal Prolapse, and Intestinal Pseudo-Obstruction in Transgenic Mice Overexpressing Hepatocyte Growth Factor/Scatter Factor

Takayama

Takagi

LaRochelle

et al. 2001

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of gastrointestinal epithelial cells in vitro;however, the physiological role of HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo function, mice were analyzed in which an HGF/SF transgene was overexpressed throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in this study (28 of 87) died by 6 months of age as a result of sporadic intestinal obstruction of unknown etiology. Enteric ganglia were not overtly affected, indicating that the pathogenesis of this intestinal lesion was different from that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse. Expression of interleukin-2 was decreased in the transgenic colon, indicating that HGF/SF may influence regulation of the local intestinal immune system within the colon. These results suggest that HGF/SF plays an important role in the development of gastrointestinal paresis and chronic intestinal inflammation. HGF/SF transgenic mice may represent a useful model for the study of molecular mechanisms associated with a subset of IBD and intestinal pseudo-obstruction. Moreover, our data identify previously unappreciated side effects that may be encountered when using HGF/SF as a therapeutic agent. (Lab Invest 2001, 81:297-305).H epatocyte growth factor/scatter factor (HGF/ SF) was first identified as a highly potent hepatocyte mitogen (Gohda et al, 1988;Nakamura et al, 1989) but is now known as a multifunctional cytokine based on its ability to stimulate proliferation, movement, and/or morphogenesis of a broad spectrum of cultured epithelial cells expressing the tyrosine kinase receptor encoded by the c-met proto-oncogene (Gherardi and Stoker, 1991;Montesano et al, 1991;Rosen et al, 1994;Rubin et al, 1991;Vande Woude, 1992;Zarnegar and Michalopoulos, 1995). HGF/SF is produced in cells of mesenchymal origin, whereas c-met is expressed in adult and embryonic epithelium, implicating HGF/SF-Met signal transduction pathways as important in the epithelial-mesenchymal interaction that occurs during embryogenesis, tissue organization, and organogenesis. Gene targeting studies have shown that HGF/SF-Met signaling is required for the normal development of liver, skeletal muscle, and placenta Schmidt et al, 1995;Uehara et al, 1995).In the fetal digestive tract, c-met transcripts were found in the epithelia of the intestinal anlagen and the villi, whereas the distribution of HGF/SF RNA showed dynamic changes during mouse development by in situ hybridization (Sonnenberg et al, 1993). Immunohistochemical analysis of temporal expression revealed that both HGF/SF and c-Met could be detected between 7 and 8 weeks of gestation in human fetal digestive tissues (Kermorgant et al, 1997). These results suggest that HGF/SF-Met signaling participates in digestive system morphogenesis. Moreover, previous studies demonstrated that HGF/SF can stimulate both esophageal ...

show abstract

Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters

Cited by 266 publications

References 28 publications

Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons

Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal

Ulcerative Proctitis, Rectal Prolapse, and Intestinal Pseudo-Obstruction in Transgenic Mice Overexpressing Hepatocyte Growth Factor/Scatter Factor

Contact Info

Product

Resources

About