Does abnormal expression of acetylcholine receptors in Hirschsprung's disease induce acetylcholine esterase positive nerve fibres?
OBJECTIVE
Alpha bungarotoxin (alpha-BTX) is a neurotoxin isolated from the venom of Bungarus multicinctus that binds specifically to the beta-subunits of nicotinic acetylcholine receptors (nAChR) on myotube membranes. The purpose of the present study was to investigate the distribution of alpha-BTX-sensitive nAChR in Hirschsprung's disease (HD) to understand the histopathological features of HD, especially the increase in acetylcholine esterase (AChE) positive nerve fibres.


METHODS
Confocal microscopy was used to study the expression of FITC (fluorescein isothiocyanate)-alpha-BTX, anti-synaptophysin (A-SY) antibody, and anti-neurofilament (A-NF) antibody to determine the distribution of nAChR and ganglion cell and nerve fibres in colon specimens from five cases of HD and three normal controls.


RESULTS
Quantitative assessment of the immunoreactivity of colonic muscle and colonic mucosal epithelium from an aganglionic segment of HD bowel demonstrated markedly increased nAChR compared with colonic muscle and colonic mucosal epithelium from a ganglionic segment of HD bowel and normal bowel (p < 0.0001, respectively), both of which have only a few positive nAChR. In colonic muscle from aganglionic and transitional segments of HD, there were many nAChR around hypertrophic nerve trunks identified by A-NF and A-SY staining.


CONCLUSIONS
We suggest that abnormal expression of nAChR in HD might be implicated in causing gastrointestinal dysmotility because of their localization around hypertrophic nerve trunks.
Kusafuka
Junichi
J
Department of Pediatric General and Urogenital Surgery, BioMedical Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Kobayashi
Hiroyuki
H
Miyahara
Katsumi
K
Lane
Geoffrey J
GJ
Sueyoshi
Noriyoshi
N
Yamataka
Atsuyuki
A
D000110:Acetylcholinesterase / Q000378:metabolism*; D002038:Bungarotoxins / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology*; D006627:Hirschsprung Disease / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D000110:Acetylcholinesterase