Does [³H]Nifedipine Label the Calcium Channel in Rabbit Myocardium?

Abstract

The ionic and drug specificities of the [³H]nifedipine binding site in rabbit cardiac homogenates were investigated. Divalent cations inhibited specific [³H]nifedipine binding in the potency order: Ni⁺² > Ca⁺² ≥ Mg⁺². Monovalent cations did not affect binding. The inorganic calcium entry blocker La⁺³ (IC₅₀ = 1.1 mM) was the most potent cation in inhibiting radioligand binding. Calcium entry blocking drugs of different chemical classes inhibited [³H]-nifedipine binding, with a rank potency order of: nifedipine >> D600 = verapamil > tiapamil > cinnarizine = prenylamine. The same potency order was observed for these drugs in inducing negative inotropic activity of isolated, electrically stimulated rabbit papillary muscle. The stereoselectivity of verapamil and D600 ((−) >> (+) isomers) in depressing papillary muscle contractions was not seen in [³H]nifedipine competition experiments. This presents an obstacle to accepting the equivalence of the [³H]nifedipine binding site with the myocardial Ca⁺² channel. It is, however, possible that the myocardial Ca⁺² channel may be associated with multiple sites of action for calcium entry blockers.