CHOLINERGIC ACTIVATION OF CL- SECRETION IN RAT COLONIC EPITHELIA

Acetylcholine receptor agonists and antagonists were used in a pharmac ological analysis to identify which muscarinic receptor(s) may be invo lved in cholinergic regulation of Cl- secretion across rat colonic muc osa in vitro. A comparative ligand binding analysis for each of the an tagonists was carried out in parallel. Both studies elicited identical rank order potencies (atropine greater than or equal to 4-diphenyl-ac etoxy-N-piperidine methiodide (4-DAMP) > pirenzepine > -dihydro-6H-pyr ido[2,3-b]]1,4]benzodiazepine-6-one (AF-DX 116). Cholinomimetic-induce d Cl- secretion was predominantly mediated by activation of muscarinic receptors in rat isolated colonic mucosa, with only a modest contribu tion from nicotinic receptors. Short circuit current responses evoked by the selective muscarinic M(1) receptor agonist )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-media ted Cl- secretion appear to belong to the M(3) class.