Prostaglandin endoperoxide and thromboxane generating systems and their selective inhibition.

Two enzyme systems and their selective inhibition are described. Microsomes from ram seminal vesicles (RSV) incubated with arachidonic acid at 22 degrees C generated a rabbit aorta contracting substance which, after rapid ether extraction, had characteristics similar to purified standard endoperoxides. Incubation of either purified endoperoxide or the product from RSV and arachidonic acid with horse platelet microsomes (HPM) yielded a more potent rabbit aorta contracting substance characterized as thromboxane A2, with a half life of 35.9 +/- 2.2 s at 37 degrees C after ether extraction. Two inhibitors, indomethacin and benzydamine exhibited selectivity for the two enzyme systems. The IC50 for benzydamine against thromboxane synthetase was 100 mug/ml and 250 mug/ml against RSV. Indomethacin showed a greater degree of selectivity with an IC50 of 5 mug/ml for the ram seminal vesicle cyclo-oxygenase compared to 100 mug/ml for thromboxane synthetase.