Effects of thromboxane synthetase inhibitors on aggregation of rabbit platelets

Thromboxane (TX) synthetase activity was selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) and sodium (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methyl-propenoate (OKY-1581) (OKYs). Their IC 50 for the rabbit platelet enzyme were found to be 11nM and 3nM respectively. Arachidonic acid (AA) or collagen induced platelet aggregation, and generated TXA 2 and prostaglandins (PGs) in rabbit platelets. OKYs inhibited platelet aggregation and TXA 2 generation without affecting PGs generation, while aspirin inhibited platelet aggregation, and TXA 2 and PGs generation. There was a parallel relation between the degree of inhibition of platelet aggregation and TXA 2 generation by OKYs, but the inhibitory effects of aspirin on platelet aggregation was related to that on both TXA 2 and PGs generation. However, OKYs and aspirin did not inhibit ADP-induced platelet aggregation which did not involve the generation of TXA 2 and PGs. These results suggested that TXA 2 generation is related to platelet aggregation induced by AA or collagen, and that the inhibitory effect of OKYs on platelet aggregation is due to the inhibition of TX synthetase.