AJP - Heart and Circulatory Physiology, Vol 242, Issue 1 19-H23, Copyright © 1982 by American Physiological Society
Interaction of verapamil with human platelet alpha-adrenergic receptors
E. S. Barnathan, V. P. Addonizio and S. J. Shattil
Platelet aggregation induced by epinephrine is an alpha-adrenergic event
and is inhibited in vitro by the calcium-channel blocker, verapamil. We
wondered whether this inhibition might be mediated by an interaction of
verapamil with platelet alpha-adrenergic receptors. 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 microM verapamil
caused a fivefold decrease in the affinity of binding of [3H]DHE to
platelet alpha-adrenergic receptors (P less than 0.001) with no change in
the number of receptors per platelet. The inhibition of binding was not
reversed by excess calcium. 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. Moreover 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 calcium flux across cell membranes, the present
studies demonstrate that verapamil also inhibits epinephrine-induced
aggregation at the level of the platelet alpha-adrenergic receptor.
