Alterations in platelet alpha 2-adrenoceptors by aspirin

Abstract

Epinephrine-induced platelet aggregation (mediated through interaction with alpha 2-adrenoceptors) is inhibited by aspirin. To determine if aspirin modulates alpha 2-adrenoceptors, we quantitated dissociation constant (KD) and maximum number of binding sites (Bmax) on isolated platelet membranes using alpha 2-antagonist 3H-yohimbine in normal subjects given 650 mg of aspirin orally. Alpha 2-receptor KD increased from 3.20 +/- 1.80 to 7.32 +/- 3.32 nM (p less than 0.02) and Bmax from 115 +/- 77 to 190 +/- 140 fmol/mg protein. To determine if these alterations in alpha 2-receptors by aspirin were mediated through circulatory or intracellular effects, intact platelets or isolated platelet membranes were incubated with aspirin for 30 minutes in vitro. In these in vitro experiments, alpha 2-receptor KD increased from 2.92 +/- 1.76 to 9.83 +/- 8.55 nM and Bmax from 140 +/- 81 to 191 +/- 129 fmol/mg protein (p less than 0.05). Oral ingestion of aspirin or incubation of aspirin with intact platelets or lysates increased (3 to 10 fold) the concentration of 1-epinephrine required for inhibition of 3H-yohimbine binding by 50% (p less than 0.05). Basal platelet cyclic AMP as well as its elevation with PGE1 or PGI2 and decrease with catecholamines were not influenced by aspirin treatment of platelets. These data indicate that aspirin decreases platelet alpha 2-receptor affinity for agonist as well as antagonist. These effects of aspirin are independent of circulatory or dynamic intraplatelet changes.