title: Tissue response selectivity of calcium antagonists is not due to heterogeneity of [3H]-nitrendipine binding sites.
abstract: [3H]-nitrendipine binding data and isolated tissue response for five calcium antagonists were evaluated in rabbit myocardium and aorta. The [3H]-nitrendipine binding site was qualitatively identical in myocardium and aorta, as the [3H]-nitrendipine KD, KIS for nicardipine and nifedipine and interactions with verapamil, D600 and diltiazem were not different in aortic and cardiac membranes prepared by similar means. In contrast, the inhibition of the Ca2+-induced contractile response in right ventricular myocardium and aortic ring segments indicated a greater than 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 greater than nifedipine greater than D600 greater than verapamil greater than diltiazem) as compared to antagonism of myocardial tissue response (D600 greater than verapamil greater than or equal to nifedipine greater than nicardipine greater than or equal to diltiazem). In heart the difference between the potency of nicardipine in binding experiments and tissue response approached 4 orders of magnitude. We conclude that tissue response selectivity of calcium antagonists is not explained by heterogeneity of [3H]-nitrendipine binding sites.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009928:Organ Specificity; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D005711:Gallopamil; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine