RU 38486 inhibits intracellular calcium mobilization and PGI2 release from human myometrium: mechanisms of action.

We previously demonstrated that the antiprogestogen RU 486, when superfused on myometrial strips, induces a rapid decrease in spontaneous uterine contractile frequency, an increase in amplitude and duration of contractions, and a concomitant decrease in 6-keto PGF(1alpha) release. In this study, we present further work on the role of calcium transients and the involvement of the PLC/PKC pathway in mediating RU 486 effects. We found no clear causal relationship between the spontaneous contractility controlled by external Ca++ concentration and 6-keto PGF(1alpha) release depending mostly on intracellular Ca++ mobilization.

Effect of the progesterone antagonist RU486 on human myometrial spontaneous contractility and PGI2 release.

We studied the effect of antiprogesterone RU 486 on spontaneous uterine contractility and PGI2 release with human myometrial strips superfused "in vitro". A decrease of PGI2 release into the superfusion medium was observed after 20 min superfusion. The inhibition was dose-dependent and reversible.

Kinetic resolution of racemic leukotriene A4 by mammalian cytosolic epoxide hydrolases.

Cytosols of rat and guinea pig liver and of human placenta were screened for their capacity to catalyze the conversion of racemic leukotriene A4 into 5S, 12R-dihydroxy-(Z,E,E,Z)-6,8,10,14-eicosatetraenoic acid (leukotriene B4). The epoxide hydrolase activities showed some specificity for the 5S,6S-oxido-(E,E,Z,Z)-7,9,11,14-eicosatetraenoic acid (LTA4) and produced mixtures of leukotriene B4 and its enantiomer containing up to 78-87% of leukotriene B4.

Racemic LTA4 methyl ester bioconversion into LTC4 methyl ester by various glutathione S-transferases.

It has been shown that various glutathione transferases can synthesize leukotriene C4, or its methyl ester, from glutathione and leukotriene A4. We questioned whether the same enzymes could be used to resolve racemic leukotriene A4 methyl ester (more easily prepared than the optically active enantiomer) and to produce leukotriene C4 methyl ester selectively. We present in this paper a study of the enantioselectivity of some rat liver glutathione transferase isozymes and of the glutathione transferase of human placenta for the leukotriene A4 methyl ester isomers.

Inhibition of platelet aggregation by human placenta.

Human placental cytosol inhibits platelet aggregation induced by high doses of collagen. The aim of this study was to investigate whether this anti-aggregating activity was caused only by the presence of various activities already described in the placenta (an ADP-consuming enzyme, a fatty acid cyclooxygenase inhibitor, and a thromboxane synthetase inhibitor) or whether another factor was present. Heating the cytosol at 50 degrees C for 6 min destroyed the inhibitor of collagen-induced aggregation.

Prostaglandin synthesis from endogenous and exogenous arachidonic acid in the rat uterus. Effect of estradiol and progesterone.

Regulation of uterine prostaglandin (PG) synthesis by steroid sex hormones was studied in female rats. Animals were ovariectomized (OVX) and received silastic implants of estradiol (E2) or progesterone (Pg); the implants were maintained for 7 days. The animals were sacrificed and their uteri homogenized at 4 degrees C.

The human placental anti-aggregating factor is neither prostacyclin, nor a prostacyclin metabolite.

Using PGH2 as substrate, we have previously demonstrated that human placenta synthesizes mainly PGE2, TxB2 and PGD2(1,2). Other reports have shown that placental tissue generates a substance which inhibits ADP-induced platelet aggregation and which was supposed to be PGI2 (3). The present study indicates that the stability of that substance is different from the stability of prostacyclin (released by umbilical artery pieces).

Effect of oestradiol 17 beta on prostaglandin biosynthesis by the uterus of ovariectomized rat and guinea pig.

In vitro prostaglandin biosynthesis by uteri of ovariectomized rats and guinea pigs treated or untreated with oestradiol 17 beta, administered subcutaneously, was measured by R.I.A.

Prostaglandin biosynthesis by the rat uterus during the oestrus cycle, temporal correlation with plasma oestradiol and progesterone concentrations, identification of 6 keto PGF1 alpha as the major metabolite.

Prostaglandin biosynthesis was studied in the rat uterus during the oestrous cycle. Uterine homogenates were incubated for 20 minutes inthe presence of exogenous substrate (2.10(-5)M).

Prostaglandin synthesis in human placenta and fetal membranes.

The conversion of exogenous arachidonic acid into prostaglandins was studied in human placenta and fetal membrane microsomes. Only one prostaglandin was formed, prostaglandin E2 (PGE2), in fetal membrane microsomes. In placental microsomes PGE2 was further transformed into 15 keto-PGE2.