Tissue response selectivity of calcium antagonists is not due to heterogeneity of [3H]‐nitrendipine binding sites

Abstract

1 [³H]-nitrendipine binding data and isolated tissue response for five calcium antagonists were evaluated in rabbit myocardium and aorta. 2 The [³H]-nitrendipine binding site was qualitatively identical in myocardium and aorta, as the [³H]-nitrendipine K_D, K_Is for nicardipine and nifedipine and interactions with verapamil, D600-and diltiazem were not different in aortic and cardiac membranes prepared by similar means. 3 In contrast, the inhibition of the Ca²⁺-induced contractile response in right ventricular myocardium and aortic ring segments indicated a > 10,000 fold selectivity of nicardipine for antagonism of vascular responses. This resulted in a different order of potency for calcium antagonist interaction with the [³H]-nitrendipine binding site in cardiac membranes (nicardipine > nifedipine > D600 > verapamil > diltiazem) as compared to antagonism of myocardial tissue response (D600 > verapamil > nifedipine > nicardipine > diltiazem). In heart the difference between the potency of nicardipine in binding experiments and tissue response approached 4 orders of magnitude. 4 We conclude that tissue response selectivity of calcium antagonists is not explained by heterogeneity of [³H]-nitrendipine binding sites.