Interaction of verapamil with human platelet alpha-adrenergic receptors

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Abstract
Platelet aggregation induced by epinephrine is an .alpha.-adrenergic event and is inhibited in vitro by the Ca-channel blocker, verapamil. Whether this inhibition might be mediated by an interaction of verapamil with platelet .alpha.-adrenergic receptors was studied. Verapamil inhibited the specific binding of [3H]dihydroergocryptine ([3H]DHE), a nonselective .alpha.-adrenergic antagonist, to intact platelets in a concentration-dependent and competitive manner. At 10 .mu.M verapamil caused a 5-fold decrease in the affinity of binding of [3H]DHE to platelet .alpha.-adrenergic receptors (P < 0.001) with no change in the number of receptors per platelet. The inhibition of binding was not reversed by excess Ca. Verapamil also inhibited the binding of a selective .alpha.2-adrenergic antagonist, [3H]yohimbine, to intact platelets and inhibited the binding of an .alpha.2-partial agonist, [3H]clonidine, to platelet membranes. There was a strong correlation between verapamil''s effect on [3H]DHE binding and its effect on epinephrine-induced aggregation (r = 0.98). Although verapamil is commonly used as an inhibitor of Ca flux across cell membranes, verapamil also inhibits epinephrine-induced aggregation at the level of the platelet .alpha.-adrenergic receptor.