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 n eural regulation of intestinal function, we examined the synthesis and breakdown of ACh in smooth muscle/myenteric plexus (SM/MP) preparatio ns from the jejunum of the rat during inflammation caused by infection with the nematode parasite Trichinella spiralis. Both total and neuro n-specific uptake of the ACh precursor [H-3]choline into SM/MP prepara tions was increased by over twofold on Day 6 postinfection. Further, a radiochemical assay of choline acetyltransferase activity showed sign ificant increase by Day 1, with peak values reached by Day 3 and maint ained without reversal thereafter. Despite the enhancement of these st eps, measurement of the conversion of [H-3]choline into [3H]ACh in SM/ MP preparations in vitro showed a nearly fourfold decrease by Day 6, i mplying a large decrease in ACh production in the inflamed jejunum. Ex amination 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 in nervation of the intestine can undergo rapid and long-lasting alterati ons during inflammation. Upregulation of major steps in the synthetic pathway for ACh was not matched by increased ACh production, suggestin g that defects in ACh packaging, storage, and granule exocytosis may a lso be present. (C) 1998 Academic Press.