Interaction of Verapamil and Other Calcium Channel Blockers with α_1- and α_2- Adrenergic Receptors

To determine the specificity of the previously demonstrated competition of verapamil with radioligand binding to α-adrenergic receptors, we examined the interaction of calcium channel blockers with α_1- and α_2-adrenergic receptors on several tissues. Verapamil competed for [³H] prazosin binding to α_1-adrenergic receptors and for [³H]yohimbine binding to α_2-adrenergic receptors in several tissues (human platelets, rat kidney and heart, and cultured muscle cells) with dissociation constants of 0.6–6 μM. The calcium channel blockers D600, D591, fendiline, and prenylamine- which are structural analogues of verapamil-also competed for [³H]yohimbine binding to human platelets. Two other calcium channel blockers, diltiazem and nifedipine, did not compete for [³H] yohimbine binding to human platelets or [³H]prazosin binding to membranes prepared from rat ventricles. We used [³H]nitrendipine binding to identify putative calcium channels on rat myocardial membranes. Nifedipine and verapamil blocked these [³H]nitrendipine-binding sites on ventricular membranes, but epinephrine and prazosin did not, indicating that the ventricular «i receptors and calcium channels are distinct. We found no specific [³H]nitrendipine binding to human platelets. We conclude that the interaction of verapamil with α-adrenergic receptors is not receptor subtype or tissue specific, that interaction with α-adrenergic receptors is not a property of all calcium channel blockers, and that the interaction of verapamil with a-adrenergic receptors and its interaction with calcium channels occur at at least two distinct sites.