Interaction of verapamil and other calcium channel blockers with α1- and α2-adrenergic receptors

Abstract

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 blocker with α1- and α2-adrenergic receptors on several tissues. Verapamil competed for [3H] prazosin binding to α1-adrenergic receptors and for [3H]yohimbine binding to α2-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 α1 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 α-adrenergic receptors and its interaction with calcium channels occur at at least two distinct sites.