Cholinergic activation of Cl- secretion in rat colonic epithelia

Abstract Acetylcholine receptor agonists and antagonists were used in a pharmacological analysis to identify which muscarinic receptor(s) may be involved in cholinergic regulation of Cl − secretion across rat colonic mucosa in vitro. A comparative ligand binding analysis for each of the antagonists was carried out in parallel. Both studies elicited identical rank order potencies (atropine ≥ 4-diphenyl-acetoxy- N -piperidine methiodide (4-DAMP) > pirenzepine > 11-[[2[(diethylamino)methyl]-1-pipiridinyl]acetyl[-5,11-dihydro-6 H -pyrido[2,3- b ]]1,4]benzodiazepine-6-one (AF-DX 116). Cholinomimetic-induced Cl − secretion was predominantly mediated by activation of muscarinic receptors in rat isolated colonic mucosa, with only a modest contribution from nicotinic receptors. Short circuit current responses evoked by the selective muscarinic M 1 receptor agonist 4-[[(3-chlorophenyl)amino]carbonyl]- N,N,N -trimethyl-2-butyn-1-aminium chloride (McN-A-343) suggest that this receptor subtype, which is thought to be neuronally sited, also plays a minor role in regulation of intestinal ion transport. The principal epithelial cell receptors responsible for acetylcholine receptor-mediated Cl − secretion appear to belong to the M 3 class.