title: Muscarinic M2 receptors in bovine tracheal smooth muscle: discrepancies between binding and function.
abstract: Previous work showing that AF-DX 116, a cardioselective muscarinic antagonist in functional experiments, does not discriminate between muscarinic receptors in bovine cardiac and tracheal membranes has been extended. In addition to AF-DX 116 we used the muscarinic antagonists, atropine, pirenzepine, 4-DAMP methobromide, gallamine, hexahydrosiladifenidol and methoctramine, in radioligand binding experiments on bovine cardiac left ventricular and tracheal smooth muscle membranes. The functional antagonism of the methacholine-induced contraction of bovine tracheal smooth muscle strips was also evaluated. An excellent correlation was found for all compounds between the binding affinities for muscarinic receptors in cardiac and tracheal smooth muscle membranes; moreover, the affinities found in cardiac membranes correspond with the pA2 values reported for atrial preparations of rat and guinea pig. However, significant and occasionally marked discrepancies were found between binding and functional affinities of these muscarinic antagonists on bovine tracheal smooth muscle.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: Roffel
authors.forename: C R
authors.initials: CR
authors.lastname: Elzinga
authors.forename: R G
authors.initials: RG
authors.lastname: Van Amsterdam
authors.forename: R A
authors.initials: RA
authors.lastname: De Zeeuw
authors.forename: J
authors.initials: J
authors.lastname: Zaagsma
mesh_terms: D000818:Animals; D002417:Cattle; D003909:Dexetimide / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
chemical_list: D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D003909:Dexetimide