抄録
Isolated rat aortae were incubated at 22°C in 1ml of Tris-buffered saline (pH 7.4). The incubation medium was changed every 10min and the amounts of PGI2 in the medium were immediately bioassayed as an inhibitory activity against rabbit platelet aggregation induced by ADP.
An addition of arachidonic acid to the medium caused the increased generation of PGI2, followed by gradual decrease even in spite of the presence of the same amount of arachidonic acid, whereas the generation from PGH2 was kept constant. The decrease of PGI2 generation from arachidonic acid was prevented by tryptophan, which was required by PG hydroperoxidase with heme compounds as a cofactor. MK-447, which was reported to exert tryptophan-like action in PG endoperoxide biosynthesis, also prevented the decrease. These results indicate that MK-447 can act as a tryptophan-like cofactor in the PGI2 generation.
When isolated rat aortae were mechanically stimulated by manual stretch before each 10min incubation, the PGI2 generation from endogenous arachidonic acid was kept fairly constant after initial transient decrease. The addition of MK-447 to the medium obviously accelerated the PGI2 generation. The present results suggest that MK-447 may be a good candidate of drugs which prevent the thrombus formation.
