Effects of indomethacin, NS-398 (a selective prostaglandin H synthase-2 inhibitor) and protein synthesis inhibitors on prostaglandin production by the guinea pig placenta

The outputs of PGF2 alpha, PGE(2) and 6-keto-PGF(1 alpha),were similar from the day 22 guinea-pig placenta and sub-placenta in culture, except for PGE (2) output from the sub-placenta which was lower. Between days 22 and 29 of pregnancy, the outputs of PGF(2 alpha), PGE(2) and 6-keto-PGF(1 alpha) dur ing the initial 2 h culture period increased 6.9-,1.1- and 3.2-fold, respec tively, from the placenta, and 2.1-,1.4- and 2.2-fold, respectively, from t he sub-placenta. Therefore, there was a relatively specific increase in PGF (2 alpha) production by the guinea-pig placenta between days 22 and 29 of p regnancy. The output of PGFM from the cultured placenta also increased betw een days 22 and 29, indicating that the increase in PGF(2 alpha) output was due to increased synthesis rather than to decreased metabolism. By compari ng the amounts of prostaglandins produced by tissue homogenates during a 1 h incubation period, it appears that there is approximately a 2-fold increa se in the amount of prostaglandin H synthase (PGHS) present in the guinea-p ig placenta between days 22 and 29. NS-398 (a specific inhibitor of PGHS-2) and indomethacin (an inhibitor of both PGHS-1 and PGHS-2) both inhibited p rostaglandin production by homogenates of day 22 and day 29 placenta. Indom ethacin was more effective than NS-398, except for their actions on PGF(2 a lpha) production by the day 29 placenta wh ore indomethacin and NS-398 were equiactive. Indomethacin and NS-398 were both very effective at inhibiting the outputs of PGF(2 alpha), PGE(2) and 6-keto-PGF(1 alpha) from the day 2 2 and day 29 placenta and sub-placenta in culture, indicating that prostagl andin production by the guinea-pig placenta and sub-placenta in culture is largely dependent upon the activity of PGHS-2. The high production of PGF(2 alpha), by the day 29 placenta is not dependent on the continual synthesis of fresh protein(s), as inhibitors of protein synthesis did not reduce PGF (2 alpha) output from the day 29 guinea-pig placenta in culture. (C) 2001 H arcourt Publishers Ltd.