A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract

Sanders, Kenton M.

doi:10.1053/gast.1996.v111.pm8690216

Cited by 909 publications

(870 citation statements)

References 16 publications

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“…The interstitial cells of Cajal in the gastrointestinal nervous system show constitutional expression of c-kit and have recently been suggested as ancestor cells for GISTs. 7,8,10,16,17 Therefore, c-kit expression in GISTs could merely reflect the constitutional c-kit expression that is maintained in the neoplastic state of tumor cells, which may be related to the Cajal cells or show differentiation toward them. 8,10 In summary, we have evaluated a series of GISTs and typical smooth muscle tumors for the expression of c-kit protein and for the mutations in exon 11 of c-kit.…”

Section: Discussionmentioning

confidence: 99%

Mutations in Exon 11 of c-Kit Occur Preferentially in Malignant versus Benign Gastrointestinal Stromal Tumors and Do Not Occur in Leiomyomas or Leiomyosarcomas

Lasota

Jasiński

Sarlomo-Rikala

et al. 1999

The American Journal of Pathology

503

320

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Gastrointestinal stromal tumors (GISTsGastrointestinal stromal tumor (GIST) is the designation for a major subset of mesenchymal tumors of the gastrointestinal tract. These tumors differ from ordinary leiomyomas and leiomyosarcomas histologically, immunohistochemically and genetically. GISTs are typically more cellular than ordinary leiomyomas and are composed of spindle or epithelioid-appearing cells. Immunohistochemically they are typically positive for CD34, the hematopoietic progenitor cell antigen, but negative for desmin, in contrast to leiomyomas and leiomyosarcomas.

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Section: Discussionmentioning

confidence: 99%

Mutations in Exon 11 of c-Kit Occur Preferentially in Malignant versus Benign Gastrointestinal Stromal Tumors and Do Not Occur in Leiomyomas or Leiomyosarcomas

Lasota

Jasiński

Sarlomo-Rikala

et al. 1999

The American Journal of Pathology

503

320

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“…The slow waves originate in the ICCs distributed in the GI tract (Dickens et al, 1999;Huizinga et al, 1995;Langton et al, 1989;Torihashi et al, 1995;Ordog et al, 1999;Ward et al, 1994). ICCs express c-kit immunoreactivity and form gap junctional connections with ICCs and with smooth muscle cells (Huizinga et al, 1997;Komuro et al, 1992;Sanders, 1996). Many types of ICC with different immunohistochemical and electrical properties, such as myenteric ICC (ICCMY), intramuscular ICC, deep muscular plexus ICC and submucosal ICC, are distributed in the GI tract .…”

Section: Discussionmentioning

confidence: 99%

“…Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal (GI) muscles that generate the rhythmic oscillations in the membrane potential known as slow waves (Huizinga et al, 1995;Sanders, 1996;Ward et al, 1994). Slow waves propagate within ICC networks, conduct into smooth muscle cells via gap junctions, and initiate phasic contractions by activating Ca 2+ entry through L-type Ca 2+ channels.…”

Section: Introductionmentioning

confidence: 99%

Effects of Transient Receptor Potential Channel Blockers on Pacemaker Activity in Interstitial Cells of Cajal from Mouse Small Intestine

Kim

Nam

Kim

2011

Molecules and Cells

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The interstitial cells of Cajal (ICCs) are pacemakers in the gastrointestinal tract and transient receptor potential melastatin type 7 (TRPM7) is a candidate for pacemaker channels. The effect of the 5-lipoxygenase (5-LOX) inhibitors NDGA, AA861, MK886 and zileuton on pacemaking activity of ICCs was examined using the whole cell patch clamp technique. NDGA and AA861 decreased the amplitude of pacemaker potentials in ICC clusters, but the resting membrane potentials displayed little change, respectively. Also, perfusing NDGA and AA861 into the bath reduced both inward current and outward current in TRPM7-like current in single ICC, respectively. But, they had no effects on Ca 2+ activated Cl -currents. The 5-LOX inhibitors MK886 and zileuton were, however, ineffective in pacemaker potentials in ICC clusters and in TRPM7-like current in single ICC, respectively. A specific TRPC3 inhibitor, pyrazole compound (Pyr3), and a specific TRPM4 inhibitor, 9-phenanthrol, had no effects in pacemaker potentials in ICC clusters and in TRPM7-like current in single ICC. These results suggest that, among the tested 5-LOX inhibitors, NDGA and AA861 modulate the pacemaker activities of the ICCs, and that the TRPM7 channel can affect intestinal motility.

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“…Interstitial cells of Cajal (ICC), which function as pacemaker cells of the gastrointestinal tract, serve as regulators of gastrointestinal motility by generation of slow waves in smooth muscle cells and by translation of enteric neuronal signals (Huizinga et al, 1995;Sanders, 1996;Ward et al, 1994). Disruption of ICC has been reported to evoke abnormal patterns of motility in several pathological conditions, including achalasia, obstructive intestinal disorders, pyloric stenosis, constipation, and diarrhea (Mostafa et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Effects of Sphingosine-1-Phosphate on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

Han

Lee

Park

et al. 2013

Molecules and Cells

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Interstitial cells of Cajal (ICC) are the pacemaker cells that generate the rhythmic oscillation responsible for the production of slow waves in gastrointestinal smooth muscle. Spingolipids are known to present in digestive system and are responsible for multiple important physiological and pathological processes. In this study, we are interested in the action of sphingosine 1-phosphate (S1P) on ICC. S1P depolarized the membrane and increased tonic inward pacemaker currents. FTY720 phosphate (FTY720P, an S1P 1,3,4,5 agonist) and SEW 2871 (an S1P 1 agonist) had no effects on pacemaker activity. Suramin (an S1P 3 antagonist) did not block the S1P-induced action on pacemaker currents. However, JTE-013 (an S1P 2 antagonist) blocked the S1P-induced action. RT-PCR revealed the presence of the S1P 2 in ICC. Calphostin C (a protein kinase C inhibitor), NS-398 (a cyclooxygenase-2 inhibitor), PD 98059 (a p42/44 inhibitor), or SB 203580 (a p38 inhibitor) had no effects on S1P-induced action. However, c-jun NH 2 -terminal kinase (JNK) inhibitor II suppressed S1P-induced action. External Ca 2+ -free solution or thapsigargin (a Ca 2+ -ATPase inhibitor of endoplasmic reticulum) suppressed action of S1P on ICC. In recording of intracellular Ca 2+ ([Ca 2+ ] i ) concentration using fluo-4/AM S1P increased intensity of spontaneous [Ca 2+ ] i oscillations in ICC. These results suggest that S1P can modulate pacemaker activity of ICC through S1P 2 via regulation of external and internal Ca 2+ and mitogenactivated protein kinase activation.

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A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract

Cited by 909 publications

References 16 publications

Mutations in Exon 11 of c-Kit Occur Preferentially in Malignant versus Benign Gastrointestinal Stromal Tumors and Do Not Occur in Leiomyomas or Leiomyosarcomas

Mutations in Exon 11 of c-Kit Occur Preferentially in Malignant versus Benign Gastrointestinal Stromal Tumors and Do Not Occur in Leiomyomas or Leiomyosarcomas

Effects of Transient Receptor Potential Channel Blockers on Pacemaker Activity in Interstitial Cells of Cajal from Mouse Small Intestine

Effects of Sphingosine-1-Phosphate on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

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