Peptidergic Nerves in Hirschsprung's Disease and Its Allied Disorders*

Abstract

To clarify the significance of peptidergic nerves in Hirschsprung's disease (aganglionosis), hypoganglionosis, and neuronal intestinal dysplasia (NID), we investigated enteric nerve responses in colonic tissues obtained from patients with these diseases. Colonic tissue specimens were obtained from 12 patients with aganglionosis, 8 patients with hypoganglionosis, and 6 patients with NID. Colon specimens from 20 patients without constipation were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerve blockers and gastrointestinal hormones. The following results were obtained: (1) Non-adrenergic inhibitory nerves were found to act on the normal human colon and to a lesser extent in colons with hypoganglionosis or NID, but had no effect on the enteric nerves in colons with aganglionosis. (2) Peptidergic neurotransmitters such as VIP, substance P, and neurotensin apparently act in the normal human colon, and to a lesser extent in the colons with hypoganglionosis or NID, but their effect was almost absent in aganglionosis. (3) VIP acts via neural mechanisms, while substance P and neurotensin may act both via nerves and also directly on the bowel smooth muscle. The diminution of action of non-adrenergic inhibitory nerves and peptidergic nerves may be largely related to the impaired motility observed in hypoganglionosis, NID and aganglionosis.

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

“…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].…”

“…Previous reports have documented the absence of inhibitory enteric neurons and ganglia in the aganglionic segment as a possible cause of pronounced colonic spasticity seen in patients with Hirschsprung's disease [8][9][10][11]. Several investigators have studied nitrergic innervation and nitric oxide (NO) activity in the ganglionic and aganglionic bowel [12][13][14].…”

Enteric nervous system and developmental abnormalities in childhood

“…No specific organic cause can be found in approximately 90% of the children, and a diagnosis of Functional or Idiopathic chronic constipation is made in these children. Even within a group of children with refractory chronic constipation, in eighty percent no known abnormality was found in their rectal suction biopsy [118]. It is estimated that 5% of all children suffer from chronic constipation lasting more than six months.…”

High affinity choline transporter immunoreactivity in rat ileum myenteric nerves

“…Histochemistry for acetylcholinesterase (AChE), the enzyme that breaks down ACh into choline and acetic acid, is used to identify cholinergic nerves but is not a selective marker for cholinergic neurons. AChE immunoreactivity (AChE-IR) is routinely used to demonstrate enlarged nerve trunks in the diagnosis of Hirschsprung's disease (Johnson et al 1995;Tomita et al 2004).…”