Muscarinic cholinergic receptors in the piebald mouse model for Hirschsprung's disease.

The contracted segment of terminal large intestine in both Hirschsprung's disease in humans and in the piebald-lethal strain of mice with congenital megacolon may result from muscarinic cholinergic receptor denervation supersensitivity. This hypothesis was tested by direct binding studies using the muscarinic receptor ligand, tritiated quinuclidinyl benzilate. There were no differences in either the receptor density, dissociation constant, or agonist/antagonist Hill coefficients in the proximal, middle, or distal colon of mice with congenital megacolon as compared with normal littermates. These data do not support the concept of denervation supersensitivity. The data support the suggestion that absence of the inhibitory neurons of the enteric nervous system accounts for the hyperexcitability of the musculature of the aganglionic terminal segment and the obstructive constriction of the segment.