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

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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.

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