We have studied the resection specimens from 5 patients with idiopathi
c megarectum and megacolon and 10 control subjects with non-obstructin
g colonic cancer. Histological staining with haematoxylin and eosin, a
nd immunocytochemical staining for protein gene product 9.5 (PGP 9.5),
S 100 protein, vasoactive intestinal polypeptide (VIP) and calcitonin
gene-related peptide (CGRP), and histochemical localization of NADPH
diaphorase was performed. The amount of VIP and CGRP present in sample
s was measured using an enzyme-linked immunosorbent assay. Patients wi
th idiopathic megarectum and megacolon showed hypertrophy of the muscu
laris mucosae and muscularis externa. The architecture of the innervat
ion as assessed by immunoreactivity for PGP 9.5 and S 100 protein appe
ared normal. There was a decrease in the density of innervation of the
longitudinal muscle in rectal tissue from patients with idiopathic me
garectum, with fewer VIP- and NADPH-diaphorase-containing nerves. In t
he muscularis mucosae and lamina propria of the rectal samples of pati
ents with idiopathic megarectum, VIP immunoreactivity was higher and m
ore NADPH-diaphorase-containing nerves were seen. CGRP-immunoreactive
nerve fibres were only seen in the myenteric plexus. No CGRP-immunorea
ctive cell bodies were seen. In summary, there is an increase in VIP a
nd nitric oxide containing fibres in the muscularis mucosae and lamina
propria and a decrease in the longitudinal muscle in rectal tissue of
patients with idiopathic megarectum. Both are NANC (nonadrenergic non
cholinergic) inhibitory transmitters in the gut and the possible relat
ionship of the changes in their density with gut function is discussed
.