EFFECTS OF ALPHA-ADRENERGIC AGENTS ON HUMAN-PLATELET AGGREGATION

Abstract

The effects of .alpha. adrenergic agonists and antagonists on human in vitro platelet aggregation were studied to characterize further the platelet .alpha. adrenergic receptor. Aggregation induced by ADP and U46619, a stable prostaglandin endoperoxide analog, was potentiated by .alpha. adrenergic agonists, an effect which was completely blocked by the .alpha. adrenergic antagonist phentolamine (1 .times. 10-6 M) but not by prazosin (1 .times. 10-6 M). The order of potency for the .alpha. adrenergic agonists in potentiating ADP-induced aggregation was clonidine .gtoreq. epinephrine > .alpha.-methylnorepinephrine > norepinephrine .mchgt. phenylephrine > methoxamine. Epinephrine-induced platelet aggregation was blocked by phentolamine, yohimbine, dihydroergotamine, clonidine and lofexidine but not by phenoxybenzamine (1 .times. 10-5 M). Clonidine and lofexidine are apparently partial agonists. The .alpha. adrenergic receptor of the platelet is apparently different from the classical postsynaptic .alpha. adrenergic receptor and more closely resembles presynaptic .alpha. adrenergic receptors.