Pathophysiological role of the cholinergic and adrenergic nerves in patients with allied disorders of Hirschsprung's disease (intestinal neuronal dysplasia and hypoganglionosis)--an in vitro experiment.
OBJECTIVE
There are no reports about the pathophysiological roles of cholinergic and adrenergic nerves in the intestines of patients with allied disorders of Hirschsprung's disease (HD) such as intestinal neural dysplasia (IND) and hypoganglionosis (Hypo). To clarify the significance of the cholinergic and adrenergic nerves in Hypo and IND, we investigated enteric nerve responses to acetylcholine (Ach) and noradrenaline (NA) in colonic tissues obtained from patients with these diseases.


METHODS
Colonic tissue specimens were obtained from 8 patients with HD (aganglionosis; 4 boys and 4 girls, aged 6 months to 3 years), 4 patients with Hypo (4 boys, aged 9 months to 3 years and 5 months), and 3 patients with IND (3 boys, aged 6 months to 3 years). Colon specimens from 8 patients without constipation (5 boys and 3 girls, aged 4 to 12 years) were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS), Ach, and NA.


RESULTS
All muscle strips showed responses to EFS. Tetrodotoxin almost abolished the EFS responses in all the muscle strips. According to these results, we ascertained that the enteric nervous system was present in all muscle strips. 1) Ach showed a contraction reaction. The frequency of the contraction reaction in normal colon was highest, followed by those in IND colon, Hypo colon, and HD colon in decreasing order. In addition, significant differences were noted between the frequency of the contraction reaction in normal colon and those in IND colon, Hypo colon and HD colon (p < 0.01, p < 0.001, p < 0.0001, respectively). 2) NA showed a relaxation reaction. The frequency of relaxation reaction in normal colon was highest, followed by those in IND colon and Hypo colon in decreasing order. HD colon showed no response. In addition, significant differences were noted between the frequency of the relaxation reaction in normal colon and those in IND colon, Hypo colon and HD colon (p < 0.05, p < 0.001, p < 0.0001, respectively). There was also a significant difference between IND colon and HD colon (p < 0.05).


CONCLUSIONS
The diminution of action of cholinergic and adrenergic nerves may be largely related to the impaired motility observed in IND, Hypo, and HD.
Tomita
Ryouichi
R
Department of Surgery, Nippon Dental University School of Dentistry at Tokyo, Japan. rtomita-ndus@mvg.biglobe.ne.jp
Howard
Edward R
ER
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D004558:Electric Stimulation; D005260:Female; D005769:Gastrointestinal Motility; D006627:Hirschsprung Disease / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin