The effects of some salicylate analogues on human blood platelets: 2. The role of platelet acetylation in the inhibition of platelet aggregation

Abstract

Aspirin, 2,3-diacetoxybenzoic acid, 2,6-diacetoxybenzoic acid and 2-propoxybenzoic acid were incubated in human platelet-rich plasma at 37°C for 5 and 10 min and the effects upon collagen induced platelet aggregation and the uptake by platelets of radioactive acetate and propionate groups from 14C-labelled analogues were studied to determine if a correlation existed between acylation of the platelet and inhibition of aggregation. Inhibition of aggregation and the uptake of radioactive label were both concentration-dependent and both increased with the time of incubation. Potency re inhibitors of aggregation was, in decreasing order, aspirin, 2,propoxybenzoic acid, 2,3-diacetoxybenzoic acid and 2,6-diacetoxybenzoic acid. Uptake of radioactive label however, was greatest with aspirin, intermediate with 2,3- and 2,6-diacetoxybenzoic acid, and lowest with 2-propoxybenzoic acid. Platelets exposed to a metabolic inhibitor (oligomycin, 10 −5M for 15 min) showed reduced uptake of labelled acetate and propionate and the degree of uptake did not correlate with the degree of inhibitory activity of the analogues on platelet aggregation. Platelet fragments produced by sonification did not take up radioactive label and chloroform: methanol extraction removed about 50% of the label from intact platelets. The results do not support the hypothesis that acetylation of platelets by aspirin is solely responsible for its inhibitory effects on aggregation but do not conflict with the suggestion that acetylation of platelets may be responsible for the persistent in vivo effects of aspirin.