title: Comparison of the muscarinic receptors in the coronary artery, cerebral artery and atrium of the pig.
abstract: The affinity of various muscarinic antagonists for the muscarinic receptors mediating contraction (induced by acetyl-beta-methylcholine) of the isolated pig coronary and basilar artery was determined in order to compare the muscarinic receptor subtype involved in the contractile response of these arteries. In order to identify the muscarinic receptor subtype(s) involved, the affinity of the antagonists for the M2 receptor present in the pig atria was also investigated. The following muscarinic antagonists were used: atropine, pirenzepine, AF-DX 116 (11-2[[2-[(diethylamino)methyl]-1- piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepin-6-one),4-DAMP(4-diphenylacetoxy-N- methylpiperidine methiodide), HHSiD (hexahydrosiladifenidol), methoctramine (N,N'-bis[6-[(2- methoxybenzyl)amino]hexyl]-1,8-octane-diamine tetrahydrochloride) and ipratropium. The order of affinity of the antagonists with respect to the muscarinic receptor in the coronary artery was clearly different from that for the muscarinic receptor in the basilar artery. The order of affinity established on the basilar artery closely resembled that for the M2 receptor in the atria. It is concluded that the muscarinic receptors on smooth muscle of the coronary and basilar arteries are not identical. The muscarinic receptor involved in the contraction of the basilar artery adheres to the M2 receptor subtype. A comparison of the selectivity of the antagonists suggests that the muscarinic receptor involved in the contraction of the coronary artery belongs to the M3 (like in exocrine glands) or M4 (as found in ileal smooth muscle) receptor subtype.
authors.affiliation: Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
authors.forename: K J
authors.initials: KJ
authors.lastname: van Charldorp
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013552:Swine
chemical_list: D008688:Methacholine Compounds; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D011189:Potassium Chloride