Cholinergic activation of Cl − secretion in rat colonic epithelia

• Published in: European journal of pharmacology 1995-02, Vol.275 (1), p.83-89
• Main Authors: O'Malley, Kate E., Farrell, Colm B., O'Boyle, Kathy M., Baird, Alan W.
• Format: Article
• Language: English
• Subjects: (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride - metabolism; (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride - pharmacology; [ 3H] N-Methylscopolamine; Animals; Binding, Competitive; Biological and medical sciences; Chlorides - metabolism; Cholinergic activation; Cholinergic Agonists; Cholinergic Antagonists; Colon - drug effects; Colon - metabolism; Colonic; Dose-Response Relationship, Drug; Epithelia; Epithelium - drug effects; Epithelium - metabolism; Fundamental and applied biological sciences. Psychology; Hexamethonium - pharmacology; In Vitro Techniques; Intestine. Mesentery; Ion transport; Ion Transport - drug effects; Male; Muscarinic Agonists; Muscarinic receptor; Parasympatholytics - metabolism; Parasympatholytics - pharmacology; Piperidines - metabolism; Piperidines - pharmacology; Pirenzepine - analogs & derivatives; Pirenzepine - metabolism; Pirenzepine - pharmacology; Radioligand Assay; Rats; Rats, Wistar; Vertebrates: digestive system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(94)00758-Y

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.