A role of nitric oxide in Hirschsprung's disease

Tomita, Ryouichi; Munakata, Keimei; Kurosu, Yasuhiko; Tanjoh, Katsuhisa

doi:10.1016/0022-3468(95)90050-0

Cited by 29 publications

(16 citation statements)

References 18 publications

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“…They found a lack of reaction of inhibitory nerves in the aganglionic bowel segments suggesting abnormal innervation of the muscle. They also observed the absence of nitric oxide as a neurotransmitter in the muscle and concluded that this was most likely to be responsible for the spasticity of the aganglionic segment [15]. Studies on the peptidergic innervation of the aganglionic intestinal segment in Hirschsprung's disease patients have also demonstrated a marked reduction in the density of nerve fibres storing vasoactive intestinal peptide (VIP), substance P (SP), enkephalin, and gastrin releasing peptide (GRP) [11,16].…”

Section: Discussionmentioning

confidence: 98%

“…Several investigators have studied nitrergic innervation and nitric oxide (NO) activity in the ganglionic and aganglionic bowel [12][13][14]. Tomita [15] examined the role of nitric oxide in Hirschsprung's disease using mechanographical techniques to study aganglionic and ganglionic bowel segments from Hirschsprung's disease patients. They found a lack of reaction of inhibitory nerves in the aganglionic bowel segments suggesting abnormal innervation of the muscle.…”

Section: Discussionmentioning

confidence: 99%

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Deficiency of purinergic P2Y receptors in aganglionic intestine in Hirschsprung’s disease

Donnell

Puri

2007

Pediatr Surg Int

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Hirschsprung's disease is characterized by the absence of ganglion cells in the distal bowel and extends proximally for varying distances. In recent years, the purinergic P2Y receptors have begun to receive much attention as they have been recognised as major ATP receptors in many regions of the body, including the intestine. ATP has long been established as an inhibitory neurotransmitter in the enteric nervous system. The aim of our study was to analyse the expression of P2Y1 and P2Y2 receptors in the intestine of patients with Hirschsprung's disease. Frozen sections were cut from rectal tissue segments taken from both the aganglionic and ganglionic regions of patients with Hirschsprung's disease, as well as tissue from normal rectal biopsies, which were used as controls. Sections were incubated overnight with P2Y1 and P2Y2 receptor antibodies and results were analysed by light microscopy. Both P2Y1 and P2Y2 immunoreactivity was absent from the submucosal and myenteric plexuses of aganglionic tissue compared to ganglionic tissue and normal controls, in which large number of immunoreactive neurons were evident, arranged in ganglia in both plexuses and positive nerve fibres, in both the smooth and circular muscles. Our results show a lack of expression of P2Y1 and P2Y2 receptors in the aganglionic gut in Hirschsprung's disease. The absence of these receptors suggests the absence of the inhibitory neurotransmitter ATP, which may help to explain the contracted state of the aganglionic gut in Hirschsprung's disease.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Deficiency of purinergic P2Y receptors in aganglionic intestine in Hirschsprung’s disease

Donnell

Puri

2007

Pediatr Surg Int

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“…In contrast, in the ganglionic segment, nNOS is abundantly present, in a pattern similar to that in the normal colon. [100][101][102][103][104][105] This deficiency could prevent smooth muscle relaxation in the aganglionic colon, thereby causing the lack of peristalsis in Hirschsprung's disease. The exposure of aganglionic colon specimens to S-nitroso-N-acetyl penicillamine (SNAP) results in the reduction of resting tension.…”

Section: Anal Sphinctermentioning

confidence: 97%

“…Antecedent infection may be associated with the impaired NO pathways observed in functional dyspepsia, colitis, and Chagas' disease. Hirschsprung's disease fl [100][101][102][103][104][105] Chagas' disease fl 95 ›, increase; fl, decrease; fi, no change; nNOS, neuronal nitric oxide synthase; GI, gastrointestinal; NANC, nonadrenergic, noncholinergic…”

Section: Perspectivesmentioning

confidence: 99%

Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract

Takahashi

2003

Journal of Gastroenterology

241

181

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It has been demonstrated that nitric oxide (NO) is a major inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter in the gastrointestinal (GI) tract. NO released in response to nerve stimulation of the myenteric plexus causes relaxation of the smooth muscle. NO is synthesized by the activation of neuronal NO synthase (nNOS) in the myenteric plexus. Released NO plays an important physiological role in various parts of the GI tract. NO regulates the muscle tone of the sphincter in the lower esophagus, pylorus, sphincter of Oddi, and anus. NO also regulates the accommodation reflex of the fundus and the peristaltic reflex of the intestine. Previous studies have shown that NOS inhibitors delay gastric emptying and colonic transit. The reduction of nNOS expression, associated with impaired local production of NO, may be responsible for motility disorders in the GI tract. There is accumulated evidence that dysfunction of NO neurons in the myenteric plexus may cause various GI diseases. These reports are reviewed and possible mechanisms of altered nNOS expression are discussed in this article. In particular, impaired nNOS synthesis of the myenteric plexus seems to be an important contributing factor to the pathogenesis of achalasia, diabetic gastroparesis, infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and Chagas' disease. Reduced NO release and/or nNOS expression are suspicious in a subset of patients with functional dyspepsia. Although the etiology of intestinal pseudo-obstruction remains unknown, it is conceivable that extrinsic denervation may upregulate nNOS expression, resulting in enhanced muscular relaxation and disturbed peristalsis. An animal model of colitis showed impaired nNOS expression in the colonic myenteric plexus. Antecedent infection may be associated with the impaired NO pathways observed in functional dyspepsia, colitis, and Chagas' disease.

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“…[7][8][9][10][16][17][18] In 1990, Bult et al 7 provided evidence that NO is released by stimulation of the NANC inhibitory nerves in the gastrointestinal tract. Recent studies have shown that NO meets most criteria for neurotransmitters, supporting a role for NO as a neurotransmitter in the gastrointestinal tract.…”

Section: L-argininementioning

confidence: 99%