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.