Murine genetic deficiency of neuronal nitric oxide synthase (nNOS^‐/‐) and interstitial cells of Cajal (W/W^v): Implications for achalasia?

Abstract

The reduction of ICC-IM and nNOS can cause dysfunction of the LES and esophageal peristalsis, whereas VIP reduction seems to have no effect. ICC-IM and nNOS deficiency might be independent relevant causes of esophageal dysfunction similar to that seen in human achalasia.

Impairment of Nitric Oxide Pathway by Intravascular Hemolysis Plays a Major Role in Mice Esophageal Hypercontractility: Reversion by Soluble Guanylyl Cyclase Stimulator

“…In fact, in vitro incubation of the esophagus body with L-NG-Nitroarginine; NG-nitro-L-Arginine (nonspecific nitric oxide synthase inhibitor) increases the EFS-induced esophageal contractile responses (Lecea et al, 2011). Previous studies showed that neuronal NO synthase gene-deficient mice display uncoordinated and higher esophagus contractions compared with wild mice (Müller et al, 2014). In this study, neurogenic contractions were greater in esophagi from PHZ compared with control mice, suggesting increased nerve-evoked acetylcholine release in the esophagus.…”

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

“…It is well known that, like other cells, the number of ICCs is controlled by several factors that regulate proliferation and death and that ICCs continuously undergo apoptosis in the GI tract of healthy individuals [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Because neurons produce Stem Cell Factor (SCF), which activates the c-kit receptor and stimulates the proliferation, survival…”

“…Studies in mice have suggested that intramuscular ICCs may play a critical role in NO-dependent neurotransmission in the GI tract and the reduction of both have been implicated as cause of dysfunction of the lower esophageal sphincter and esophageal peristalsis in nNOS -/-and ICC -/-mice [19,20]. Decreased nitrergic innervation and loss of ICCs have been observed in idiopathic achalasia and those factors, in conjunction, have been considered to be implicated in such pathological process [21,22].…”

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine

“…The interstitial cells of Cajal (ICCs) are the pacemaker cells of GI movement [15,16]. Therefore, loss of ICCs is strongly associated with several human GI motility disorders [17][18][19][20]. However, there are few reports of the efficacy of Rikkunshito on ICCs in murine small intestine.…”