title: Calcium channel agonist and antagonist binding in a highly enriched sarcolemma preparation obtained from canine ventricle.
abstract: The purpose of the present study was to characterize the binding of the Ca2+ channel agonist (+/-)[3H]Bay K 8644 in a highly enriched cardiac membrane preparation and to examine its interactions with other Ca2+ channel ligands. Scatchard analysis showed that (+/-)[3H]Bay K 8644 displayed some 265-fold less affinity for its receptor than did the Ca2+ channel antagonist (+)[3H]PN200-110. Furthermore, (+/-)[3H]Bay K 8644 binding site density was significantly less than that seen for (+)[3H]PN200-110. Kinetic analysis of (+/-)[3H]Bay K 8644 binding revealed biphasic association and dissociation rates. The Ca2+ channel antagonist MDL 12,330A stimulated both (+)[3H]PN200-110 and (+/-)[3H]Bay K 8644 binding by effects on Kd. In contrast, diltiazem inhibited (+)[3H]PN200-110 binding but had no effect on (+/-)[3H]Bay K 8644 binding. Both MDL 12,330A and diltiazem inhibited Ca2+-dependent contraction in rat aortic rings but the combination of these two drugs was less than additive in this regard. We conclude that the binding profile of (+/-)[3H]Bay K 8644 results from the racemic nature of this ligand and that MDL 12,330A and diltiazem interact at sites distinct from one another on or around the slow voltage-dependent Ca2+ channel.
authors: Department of Physiology, Baylor College of Medicine, Houston, Texas.
authors: D
authors: D
authors: Rampe
authors: T
authors: T
authors: Poder
authors: Z Y
authors: ZY
authors: Zhao
authors: W P
authors: WP
authors: Schilling
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D017275:Isradipine; D010069:Oxadiazoles / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007097:Imines; D010069:Oxadiazoles; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C014925:RMI 12330A; D004110:Diltiazem; D017275:Isradipine