Enhanced prostacyclin generation by phenolic compounds acting as a tryptophan-like cofactor of PG hydroperoxidase

Abstract

Isolated rat aortae were incubated at 22°C in tris-buffered saline (pH 7.4). The incubation medium was changed every 10 min, and the amounts of prostacyclin (PGI 2) in the medium were immediately bioassayed as an inhibitory activity against rabbit platelet aggregation induced by ADP. The addition of arachidonic acid to the medium increased the generation of PGI 2 but this was followed by a gradual decrease even in the presence of the same amount of arachidonic acid. The decrease of PGI 2 generation from exogenous arachidonic acid was prevented by tryptophan, which is required by PG hydroperoxidase with heme compound as cofactors. MK-447 and its analogues, which are phenolic compounds and exerted tryptophan-like action on the PG endoproxide biosynthesis by bovine seminal vesicle microsomes, also prevented the decrease of PGI 2 generation in isolated rat aortae. The phenolic compounds enhanced PGI 2 generation from endogenous arachidonic acid. These results indicate that theh phenolic compounds enhanced PGI 2 generation in vascular tissue, acting as a tryptophan-like cofactor of PG hydroperoxidase.