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Abstract
Human blood platelets display alpha2-adrenergic receptors, which promote platelet aggregation and inhibit the adenylate
cyclase. We investigated the effects of the antihypertensive agent clonidine and its
analogue para-aminoclonidine on this receptor in the intact human platelet to determine
their pharmacological effects and their ability to bind to the receptor by radioligand
displacement. Both agents potentiated platelet aggregation induced by a submaximal
concentration of ADP. Epinephrine-induced aggregation, on the other hand, was antagonized
by clonidine and para-aminoclonidine in a dose-dependent fashion. Both agents inhibited
the accumulation of cyclic AMP in platelets exposed to prostaglandin E1 and a phosphodiesterase inhibitor, but to a lesser extent than the inhibition caused
by epinephrine. Both antagonized this excess inhibitory action of epinephrine. Clonidine
and para-aminoclonidine blocked the binding of [3H]yohimbine (a selective alpha2-adrenergic antagonist) to intact platelets with half-maximal effects at 0.3 and 0.7
μM, respectively. No evidence for the existence of a second class of binding sites
with high affinity for clonidine was seen in intact platelets, either by this technique
or by direct binding of [3H]clonidine. It is concluded that these two agents are partial agonists for the alpha2-adrenergic receptors on blood platelets and that this receptor exists predominantly
in the low-affinity state in the intact cell.
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Article info
Publication history
Accepted:
July 12,
1983
Received:
February 15,
1983
Identification
Copyright
© 1983 Published by Elsevier Inc.
