CHOLINERGIC AGENTS MODULATE TRANSPORT IN THE ISOLATED, PERFUSED ILEUM

The mammalian small intestine is extensively innervated by cholinergic nerve fibers, including projections to the muscular and submucosal la yers. This study tested the hypothesis that cholinergic agents modulat e ileal transport independent of alterations in intestinal vascular re sistance and motility. Ten-centimeter segments of rabbit ileum (n = 32 ) were vascularly perfused ex vivo with a physiologic electrolyte solu tion containing red cells. The lumen was perfused with an electrolyte solution containing [C-14]polyethylene glycol. Net fluxes of water, so dium, and chloride were calculated during three 20-min periods: basal, drug infusion, and recovery. Agents infused at a final arterial conce ntration of 10(-5) mole/liter included acetylcholine, atropine, and he xamethonium. Measured perfusion pressure reflected changes in vascular resistance, Recovery calculations controlled for motility effects. Ac etylcholine caused significant secretion of water, sodium, and chlorid e (P < 0.05). The infusion of atropine or hexamethonium alone had no e ffect. Atropine but not hexamethonium prevented the prosecretory effec t of acetylcholine. There were no significant changes in perfusion pre ssure or C-14 recovery for any infused agent. Acetylcholine-induced il eal secretion is (1) mediated via atropine-sensitive muscarinic cholin ergic receptors, (2) independent of extraintestinal neural pathways, a nd (3) independent of changes in vascular resistance or motility. Thes e data support the hypothesis that acetylcholine influences ileal tran sport directly, independent of alterations in vascular resistance and motility. (C) 1995 Academic Press, Inc.