Abnormalities of the colonic regulatory peptides in Hirschsprung's disease

We describe here a depletion of peptide containing nerves and cells in Hirschsprung's disease, in comparison with specimens of bowel taken from age-matched neonates with no evidence of chronic constipation. VIP content in the diseased specimens was reduced by almost 80%, from 110/+-10.6 (mean +/- SEM) pmol VIP/g wet weight of tissue in controls to 23.8 +/- 3.5 pmol/g in the mid-portion of the diseased specimens. In addition, the numbers of enteroglucagon and somatostatin cells in the mucosa were significantly reduced in the aganglionic portions. Enteroglucagon cells were reduced from 55 +/- 7 in controls to 27 +/- 2 in proximal portions rising to 44 +/- 3 and 49 +/- 4 cells/mm2 in middle and distal areas. Somatostatin cell numbers also fell, from 5.5 +/- 1.9 to 1.8 +/- 0.8, 2.5 +/- 0.7 and 3.8 +/- 0.9 cells/mm2 in similar areas. Further investigation of the abnormalities of the diffuse neuroendocrine system in Hirschsprung's disease may help in understanding the nature of this condition and provide additional information on the role of these peptides in the control of gut function.