Cholinergic activation of Cl- secretion in rat colonic epithelia.
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 > or = 4-diphenyl-acetoxy-N-piperidine methiodide (4-DAMP) > pirenzepine > 11-[[2[(diethylamino)methyl]-1-pipiridinyl]acetyl[5,11- dihydro-6H-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 M1 receptor agonist 4-[[(3-chlorophenyl)amino]carbonyl]-N,N,N-trimethyl-2-butyn-1-a minium 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 M3 class.
O'Malley
K E
KE
Department of Pharmacology, University College Dublin, Belfield, Ireland.
Farrell
C B
CB
O'Boyle
K M
KM
Baird
A W
AW
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002712:Chlorides / Q000378:metabolism*; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D002712:Chlorides; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D018721:Muscarinic Agonists; D010276:Parasympatholytics; D010880:Piperidines; D018738:Hexamethonium; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C048593:otenzepad