Acetylcholine metabolism in the inflamed rat intestine

Acetylcholine (ACh) is a major neurotransmitter in the enteric nervous system. Since increasing evidence suggests that inflammation alters neural regulation of intestinal function, we examined the synthesis and breakdown of ACh in smooth muscle/myenteric plexus (SM/MP) preparations from the jejunum of the rat during inflammation caused by infection with the nematode parasite Trichinella spiralis. Both total and neuron-specific uptake of the ACh precursor [3H]choline into SM/MP preparations was increased by over twofold on Day 6 postinfection. Further, a radiochemical assay of choline acetyltransferase activity showed significant increase by Day 1, with peak values reached by Day 3 and maintained without reversal thereafter. Despite the enhancement of these steps, measurement of the conversion of [3H]choline into [3H]ACh in SM/MP preparations in vitro showed a nearly fourfold decrease by Day 6, implying a large decrease in ACh production in the inflamed jejunum. Examination of acetylcholinesterase in the rat jejunum showed decreased histochemical staining intensity in the muscle wall, and quantitative evaluation showed significantly decreased (>50%) acetylcholinesterase activity in SM/MP preparations. These results show that cholinergic innervation of the intestine can undergo rapid and long-lasting alterations during inflammation. Upregulation of major steps in the synthetic pathway for ACh was not matched by increased ACh production, suggesting that defects in ACh packaging, storage, and granule exocytosis may also be present.