Synthesis of prostaglandin E2 in rat liver

We have investigated whether rat liver microsomes can release prostaglandins and determined the 'optimal conditions' for the in vitro synthesis of PGE2. We also studied the effect of the oral administration of indomethacin, piroxicam and ibuprofen on PGE2 release ex vivo. The drugs were administered to animals at high doses for one or three consecutive days and the animals were killed 24 h after the first or the third administration. The increased PGE2 synthesis observed for indomethacin and piroxicam (animals treated for three consecutive days) could be explained by the depression of cytochrome P-450 observed in the same animals. Cytochrome P-450 could modulate the activity of eicosanoids derived from cyclooxygenase. Moreover the different inhibition of PG synthesis exhibited by these drugs could lead to a different rise in concentration of arachidonic acid in microsome membranes and contribute to an increased PGE2 synthesis.