Effects of diltiazem and verapamil on (+)-PN 200-110 binding kinetics in dog cardiac membranes.
The effects of d-cis-diltiazem (diltiazem) and verapamil on 1,4-dihydropyridine binding to dog cardiac membranes were studied in competition, saturation and kinetic binding experiments with [3H](+)-PN200-110. Diltiazem increased [3H](+)-PN200-110 binding with an observed maximal effect at 50 microM, while verapamil decreased [3H](+)-PN200-110 binding in a dose-dependent manner. Scatchard analysis of saturation binding data revealed that diltiazem (50 microM) increased the maximal binding site density and verapamil (100 microM) increased the dissociation constant (KD) of [3H](+)-PN200-110 binding. The kinetic experiments demonstrated that diltiazem significantly reduced both the association and the dissociation rate of [3H](+)-PN200-110 binding, resulting in no significant change in the apparent KD. In contrast, verapamil accelerated dissociation and slowed down association of [3H](+)-PN200-110 binding. Diltiazem appears to alter both the number of [3H](+)-PN200-110 binding sites and the characteristics of [3H](+)-PN200-110 binding.
Miwa
K
K
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Miyagi
Y
Y
Araie
E
E
Sasayama
S
S
D000494:Allosteric Regulation; D000818:Animals; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels; D004095:Dihydropyridines / Q000378:metabolism*; D004110:Diltiazem / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D017275:Isradipine; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013696:Temperature; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D011978:Receptors, Nicotinic; D014700:Verapamil; D004110:Diltiazem; D017275:Isradipine