Interaction of Verapamil and Other Calcium Channel Blockers with ax - and a 2 - Adrenergic Receptors

To determine the specificity of the previously demonstrated competition of verapamil with radioligand binding to a-adrenergic receptors, we examined the interaction of calcium channel blockers with aiand a2-adrenergic receptors on several tissues. Verapamil competed for [H] prazosin binding to ai-adrenergic receptors and for [H]yohimbine binding to a2-adrenergic receptors in several tissues (human platelets, rat kidney and heart, and cultured muscle cells) with dissociation constants of 0.6-6 (JM. The calcium channel blockers D600, D591, fendiline, and prenylamine— which are structural analogues of verapamil—also competed for [H]yohimbine binding to human platelets. Two other calcium channel blockers, diltiazem and nifedipine, did not compete for [H] yohimbine binding to human platelets or [H]prazosin binding to membranes prepared from rat ventricles. We used [H]nitrendipine binding to identify putative calcium channels on rat myocardial membranes. Nifedipine and verapamil blocked these [H]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 [H]nitrendipine binding to human platelets. We conclude that the interaction of verapamil with a-adrenergic receptors is not receptor subtype or tissue specific, that interaction with a-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. (Circ Res 52: 226-231, 1983)