Studies on cholinergic nerve function of the aganglionic colon in murin model

Abstract

The true role of the extrinsic cholinergic nerve fibers proliferating abundantly in the aganglionic colon of Hirschsprung's disease has not yet been established. Electrophysiological and pharmacological studies using superfusion method were carried out on rectal muscle strips of piebald lethal mice, one of murine models of Hirschsprung's disease and their siblings as a control. The muscle strips were preincubated with [3H] choline in Krebs solution. The contractions and the release of [3H] acetylcholine evoked by electrical transmural stimulation of the muscle strips were measured. In addition, the contractility of muscle strips treated with acetylcholinesterase blocking agents were recorded. In the aganglionic colon, as in the normal colon, the release of [3H] acetylcholine evoked by electrical transmural stimulation was recognized. However, no contractions were evoked in the aganglionic colon. The uptake of [3H] choline in the aganglionic colon was larger than in the normal colon presumably due to the proliferated extrinsic cholinergic nerve fibers. On the other hand, the release of [3H] acetylcholine evoked by electrical transmural stimulation was smaller in the aganglionic colon. In the aganglionic colon, no contractions were evoked by acetylcholinesterase blocking agents, indicating that there is no spontaneous release of acetylcholine. In the presence of low concentration of acetylcholinesterase blocking agents, the form of contractions evoked by electrical transmural stimulation in the aganglionic colon was different from those in the normal colon. These results have indicated that in the murine aganglionic colon, the proliferated extrinsic cholinergic nerve fibers may not directly regulate the smooth muscles through the functional neuro-muscular junction. In conclusion, the proliferated extrinsic cholinergic nerve fibers is not related to the narrowing of the aganglionic colon.