PEPTIDERGIC NERVES IN HIRSCHSPRUNG DISEASE AND ITS ALLIED DISORDERS

To clarify the significance of peptidergic nerves in Hirschsprung's di sease (aganglionosis), hypoganglionosis, and neuronal intestinal dyspl asia (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 hyp oganglionosis, and 6 patients with NID. Colon specimens from 20 patien ts without constipation were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulatio n (EFS) of the adrenergic and cholinergic nerve before and after treat ment with various autonomic nerve blockers and gastrointestinal hormon es. The following results were obtained: (1) Non-adrenergic inhibitory nerves were found to act on the normal human colon and to a lesser ex tent in colons with hypoganglionosis or NID, but had no effect on the enteric nerves in colons with aganglionosis. (2) Peptidergic neurotran smitters such as VIP, substance P, and neurotensin apparently act in t he normal human colon, and to a lesser extent in the colons with hypog anglionosis or NID, but their effect was almost absent in aganglionosi s. (3) VIP acts via neural mechanisms, while substance P and neurotens in may act both via nerves and also directly on the bowel smooth muscl e. The diminution of action of non-adrenergic inhibitory nerves and pe ptidergic nerves may be largely related to the impaired motility obser ved in hypoganglionosis, NID and aganglionosis.