title: Allosteric interactions of three muscarine antagonists at bovine tracheal smooth muscle and cardiac M2 receptors.
abstract: The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fast (half life less than 1 min) and was slowed by the cardioselective muscarine antagonists, gallamine, methoctramine and AF-DX 116, concentration dependently. [3H]Dexetimide dissociation from tracheal muscarine receptors was biphasic, with a fast phase (half-life less than 1 min) followed after 4-5 min by a slow phase (half-life = 38.5 min). The fast component, but not the slow component, was slowed by the muscarine antagonists with concentration dependencies very similar to those found in the heart. We conclude from these data that the major population of tracheal smooth muscle muscarine receptors resembles the cardiac M2 type not only with respect to equilibrium binding affinities but also with respect to the secondary, allosteric binding site on the muscarine receptor. The results also imply that the cardiac receptor subtype is much more sensitive to allosteric modulation than the glandular/smooth muscle receptor subtype.
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: H
authors.initials: H
authors.lastname: Meurs
authors.forename: J
authors.initials: J
authors.lastname: Zaagsma
mesh_terms: D000818:Animals; D002417:Cattle; D003909:Dexetimide / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
chemical_list: D003959:Diamines; D008565:Membrane Proteins; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D003909:Dexetimide; C054938:methoctramine; C048593:otenzepad; D005703:Gallamine Triethiodide