Qualitative and quantitative analysis of muscarinic acetylcholine receptors in the piebald lethal mouse model of Hirschsprung's disease.

Cholinergic innervation in the aganglionic bowel of the piebald lethal mouse model of Hirschsprung's disease was investigated by analysis of muscarinic acetylcholine receptors before and after administration of hexamethonium. After hexamethonium administration in the normal rectum, the maximum specific binding (Bmax) of [3H]quinuclidinyl benzilate increased from 196.6 to 346.2 fmol/mg protein without affecting the dissociation constant. This increase of muscarinic acetylcholine receptors was associated with a decrease in the 50% effective dose (ED50) of contractile response to oxotremorine from 3.8 X 10(-7) M to 6.5 X 10(-8) M. In the aganglionic rectum, hexamethonium administration did not change the Bmax (166.4 fmol/mg protein) or dissociation constant value. The ED50 of contractile response to acetylcholine and oxotremorine (4.3 X 10(-8) M, 6.5 X 10(-8) M) was lower than that in the normal rectum (1.9 X 10(-7) M, 2.0 X 10(-7) M), but it was not changed by hexamethonium. It is concluded that cholinergic innervation is congenitally absent in the aganglionic rectum in piebald lethal mice.