Evidence for multiple receptor sites within the putative calcium channel

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Abstract
[3H]-Nimodipine, a potent calcium channel blocker, binds to an apparently homogeneous population of receptors in guinea-pig brain membranes (KD=0.62 nM, Hill coefficient}1.0). Diltiazem (10−5 M) lowers the KD for [3H]-nimodipine by a factor of 3 without changing the maximum number of binding sites. Diltiazem decreased the dissociation rate constant of the nimodipine-receptor complex from 0.18 min−1 to 0.049 min−1 and altered the pharmacological profile as revealed by displacement studies with (−) and (+) verapamil, (−) and (+) prenylamine and 1,4 dihydropyridines. In conclusion [3H]-nimodipine binding can be utilized as a tool to evaluate complex molecular interactions between calcium channel blockers.