Characterization of [3H]nifedipine binding sites in rabbit myocardium

A specific, high affinity (KD 1.8 nM) binding site for the calcium entry blocking drug [3H]nifedipine was identified in homogenates of rabbit myocardium. [3H]Nifedipine binding was rapid (t1/2 3 min) and reversible (t1/2 11 min). Calcium entry blockers with different chemical structures competed with [3H]nifedipine binding in the potency order: nifedipine much greater than D600 = verapamil greater than tiapamil greater than cinnarizine = prenylamine. Diltiazem and perhexiline did not significantly inhibit [3H]nifedipine binding. The potencies of these drugs to inhibit binding were similar to their abilities to depress contractions of the isolated rabbit papillary muscle. The stereoselectivity of D600 and verapamil ((-)-much greater than (+)-isomers) as inhibitors of papillary muscle contractions was not apparent in [3H]nifedipine competition experiments. The slopes of the concentration-inhibition curves for D600 and verapamil were significantly less than for nifedipine. It is concluded that [3H]nifedipine may be labelling part of the myocardial Ca2+ channel, and that verapamil-like substances and nifedipine differ in their mode of interaction with this binding site.