title: Evidence for the binding of beta-adrenoceptor blockers to microsomal Na+/K+-ATPase in guinea pig heart preparations.
abstract: We reported in a previous study that beta-adrenoceptor blockers inhibit the Mg2+-dependent ATP-hydrolytic function of Na+/K+-ATPase. To determine if this action is a result of binding of beta-blockers to the receptor sites that bind the digitalis glycosides, we performed displacement binding assays of eight beta-blockers with [3H]-ouabain (OUA) in guinea pig myocardial microsomal preparations. In the first series of experiments, 10-200 microM of the beta-blockers were displaced with 250 nM OUA. In the second set of experiments, 10-500 nM of OUA was displaced using 200 microM of the beta-blockers. The drugs showed concentration-dependent receptor occupancy at the different OUA levels. Propranolol (PPN), metoprolol (MTP), and sotalol (STL) showed the strongest binding; nadolol (NDL), indenolol (IDN), and atenolol (ATN) had intermediate binding; carazolol (CRZ) and celiprolol (CLP) had the weakest binding properties. The results suggest that beta-blockers may compete for the same binding sites with ouabain in their inhibition of the Na+/K+-ATPase. These actions may contribute to the mechanism for some of their cardiac effects, especially their proarrhythmic and arrhythmogenic actions.
authors.affiliation: Department of Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: A A
authors.initials: AA
authors.lastname: Almotrefi
authors.forename: C
authors.initials: C
authors.lastname: Basco
authors.forename: A
authors.initials: A
authors.lastname: Moorji
authors.forename: N
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase