1,4‐Dihydropyridine Ca²⁺ channel antagonists and activators: A comparison of binding characteristics with pharmacology

Abstract

Abstract This comparison of the binding characteristics and pharmacology of 1,4‐dihydropyridines indicates that the high‐affinity binding sites studied in cardiac and smooth muscle cells represent a major site of action of these drugs, and that this site is the Ca 2+ channel or a closely related protein. Electrophysiological studies suggest that the effects of both Ca 2+ channel inhibitors and activators are voltage dependent. The apparent lack of agreement between the equilibrium dissociation constants for [ 3 H]1,4‐dihydropyridines and their potency in cardiac muscle may be due to conformational modifications that occur in the 1,4‐dihydropyridine binding site as a result of voltage or other changes during membrane isolation. The selective effect of 1,4‐dihydropyridines for vascular smooth muscle relative to cardiac muscle may be explained, in part, by differences in membrane potentials and Ca 2+ channel regulatory mechanisms and, in part, by differences in receptor structure. 1,4‐Dihydropyridine antagonists and activators appear to bind to a common site that is not the same as the binding site for nondihydropyridine Ca 2+ channel antagonists.