Decreased tyrosine kinase C expression may reflect developmental abnormalities in Hirschsprung's disease and idiopathic slow-transit constipation.
BACKGROUND
Some patients with Hirschsprung's disease have refractory constipation following excision of aganglionic bowel, as do patients with idiopathic slow-transit constipation (STC). Gut motility depends on enteric neuronal development in response to expression of trophic factors and their receptors. Recent studies indicate the importance of neurotrophin 3 (NT-3) and its high-affinity receptor tyrosine kinase C (trk C) in enteric neuronal development.


METHODS
Blinded quantitative immunohistochemical analysis of colon from patients with Hirschsprung's disease (aganglionic, hypoganglionic and normoganglionic) (n = 5), STC (n = 6) and appropriate age-matched control tissues (n = 5) was performed for NT-3 and trk C. Sural nerve morphometry and immunostaining were undertaken in three patients with STC who had abnormalities on limb autonomic and sensory testing.


RESULTS
A significantly higher proportion of submucous plexus neurones was trk C immunoreactive in control infant than adult colon (mean(s.e.m.) 73(9) versus 16(3) per cent of the total; P < 0.001), in accord with a role in development. The proportion of submucous plexus trk C-immunoreactive neurones was reduced in colon from patients with Hirschsprung's disease (28(7) per cent of total in normoganglionic Hirschsprung's disease; P < 0.007 versus infant controls) and STC (10(1) per cent of total; P = 0.053 versus adult controls). No abnormalities of STC sural nerves were detected by morphometry or immunostaining.


CONCLUSIONS
Decreased trk C expression may reflect developmental abnormalities in Hirschsprung's disease and idiopathic STC. Trk C activation by NT-3 or drugs may provide novel treatments. Presented in abstract form to the Pacific Association of Pediatric Surgeons, Las Vegas, Nevada, USA, May 2000
Facer
P
P
Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Knowles
C H
CH
Thomas
P K
PK
Tam
P K
PK
Williams
N S
NS
Anand
P
P
D000328:Adult; D000368:Aged; D002675:Child, Preschool; D003108:Colonic Diseases / Q000209:etiology / Q000378:metabolism; D003248:Constipation / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005772:Gastrointestinal Transit / Q000502:physiology; D006627:Hirschsprung Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020933:Neurotrophin 3 / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism*; D013497:Sural Nerve / Q000378:metabolism
D020933:Neurotrophin 3; D020812:Receptor, trkC