title: Characteristics of the phenylalkylamine binding site in canine cardiac sarcolemmal membranes.
abstract: We have investigated the phenylalkylamine binding site in canine cardiac sarcolemmal preparations using (-)-[3H]-desmethoxyverapamil as the labeled ligand. Radioligand binding experiments were carried out in 10 mM Hepes (Na+) buffer and 1 mM EGTA, at pH 7.4 and 20 degrees C. A single high affinity binding site for (-)-[3H]-desmethoxyverapamil was identified both by saturation and competition binding experiments. Several phenylalkylamine derivatives such as (-)-D600, (+)-D600, verapamil and (+)-desmethoxyverapamil completely inhibited (-)-[3H]-desmethoxyverapamil binding with the following order of potency: (-)-desmethoxyverapamil greater than (-)-D600 greater than verapamil greater than (+)-desmethoxyverapamil = (+)-D600. In contrast to this, ronipamil, a new long acting phenylalkylamine derivative, produced only a 70% inhibition. Diltiazem also completely inhibited (-)-[3H]-desmethoxyverapamil binding to canine cardiac sarcolemma while nifedipine displaced only 70% of binding. (-)-[3H]-desmethoxyverapamil binding was also inhibited by Ca++ and Mg++. These data suggest the presence of a saturable, reversible and stereoselective phenylalkylamine binding site in canine cardiac sarcolemmal preparations which may be a receptor for the phenylalkylamine Ca++ channel inhibitors.
authors.affiliation: Departement de Pharmacologie, Faculté de Médecine, Université de Montréal, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Dumont
authors.forename: J S
authors.initials: JS
authors.lastname: Williams
authors.forename: P L
authors.initials: PL
authors.lastname: Vaghy
authors.forename: A
authors.initials: A
authors.lastname: Schwartz
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels; D004285:Dogs; D007536:Isomerism; D008274:Magnesium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions; D014700:Verapamil / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D015220:Calcium Channels; D011978:Receptors, Nicotinic; C043184:4-desmethoxyverapamil; D014700:Verapamil; D008274:Magnesium; D002118:Calcium