Comparative effects of aspirin and diflunisal on prostaglandin synthetase from human platelets and sheep seminal vesicles.

1. We have compared the effects of diflunisal on prostaglandin (PG) synthetase from human platelets and sheep seminal vesicles (SSV) by measuring malonaldehyde, PG products, and rabbit aorta contraction. 2. Aspirin inhibits PG synthetase by covalently acetylating the enzyme. Inhibition is dependent on time and aspirin concentration. Aspirin is 37-fold more potent in inhibiting enzyme in human platelets compared with enzyme from SSV. 3. Diflunisal inhibits PG synthetase from intact human platelets and SSV equally (50% inhibition at 3-5 micronM). The drug does not covalently modify the enzyme, and inhibition is not time dependent. Diflunisal probably acts at a site similar to aspirin since the drug will inhibit acetylation of the enzyme by aspirin. 4. The results suggest that diflunisal is relatively less inhibitory to platelet function than is aspirin.