The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC.

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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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To assess the pharmacophysiological significance of the enteric nervous system and the responses of the human lower esophageal sphincter (LES) to motilin and cisapride, the mechanical responses of esophageal tissues from six patients with esophageal cancer and seven patients with gastric cancer were investigated. Circular muscle reactions were recorded to evaluate the in vitro esophageal responses to electrical field stimulation (EFS), motilin, and cisapride, evoking the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. The findings of this study revealed that: cholinergic nerves are mainly involved in the regulation of enteric nerves in the steady state, while non-adrenergic non-cholinergic (NANC) inhibitory nerves also exist; motilin may act both via nerves and also directly on the LES smooth muscle; and cisapride releases acetylcholine from the end of the postganglionic fiber of the cholinergic nerve in human LES thereby inducing contraction of the LES. These results suggest that cholinergic and NANC inhibitory nerves play an important role in human LES, and that motilin and cisapride is clinically useful for improving the impaired LES of patients with gastroesophageal reflux.

A few reports in the literature have discussed the histologic criteria for the diagnosis of allied diseases of Hirschsprung's disease in adults, and studies report that intestinal neuronal dysplasia (IND) in adults may develop from IND in infants. The aim of this study was to examine the differences between the histological findings of IND in infants and those in adults, and to assess whether allied diseases of Hirschsprung's disease (HD) in adults should be considered as congenital or acquired diseases. For these purposes, we studied nine adult patients with severe constipation, and an adult patient with acute intestinal obstruction. We routinely examined the patients using barium enema, anorectal manometry and rectal mucosal biopsy. However, in patients suspected of allied diseases, we carried out full-thickness rectal biopsies. In seven operated cases, we also examined resected intestines. The tissue samples were examined using AChE-staining, NADPH-diaphorase staining, HE-staining, and silver impregnation. Histologically, we diagnosed two males as having HD, two males as having IND, five patients (two males and three females) as having hypoganglionosis, and one female as having a degeneration of the intramural plexus. The following conclusions were drawn: 1) Inflammations such as ulcerative colitis or ischemic colitis may cause IND TYPE B in adults whose histological findings are similar to those generally seen in infants; 2) It is suggested that IND is closely related to hypoganglionosis; 3) In hypoganglionosis, a patient with findings of elevated AChE-positive nerve fibers in the mucosa and AChE-positive nerve fibers in an arterial wall may belong to a subtype of IND; 4) Most of the allied diseases of HD in adults may occur as an acquired disease, not as a congenital disease.