title: Effects of Bay k 8644, a dihydropyridine analog, on [3H]nitrendipine binding to canine cardiac sarcolemma and the relationship to a positive inotropic effect.
abstract: Equilibrium dissociation constants of Bay k 8644, a calcium agonist, and nitrendipine, a calcium antagonist, were determined in canine cardiac sarcolemma. The equilibrium dissociation constant for Bay k 8644 was compared to the concentration that produced a fifty percent increase, and the equilibrium dissociation constant for nitrendipine was compared to the concentration that produced a fifty percent decrease, in contractile force in canine heart trabecular muscle. Both saturation and inhibition binding data suggest that Bay k 8644 and nitrendipine bind to and compete for a high affinity dihydropyridine-binding site present in isolated cardiac sarcolemma preparations. The equilibrium dissociation constant (7-10 nM) and concentration that produced a fifty percent increase in contractile force in the canine trabecular muscle (30 +/- 8 nM) of Bay k 8644 were in a similar concentration range, but the equilibrium dissociation constant (0.29 +/- 0.025 nM) of nitrendipine binding was more than a thousand-fold lower than the concentration that produced a fifty percent decrease in contractile force in canine trabecular muscle (613 +/- 109 nM). These data suggest that binding of Bay k 8644 to high affinity binding sites is pharmacologically relevant, and is related to a positive inotropic effect.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001667:Binding, Competitive; D004285:Dogs; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009568:Nitrendipine; D012508:Sarcolemma / Q000378:metabolism*; D013268:Stimulation, Chemical
chemical_list: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D009543:Nifedipine