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). By GC-MS and multiple ion-monitoring, we have shown the presence of 6-keto-PGF1 alpha (the stable metabolite of PGI2) in the umbilical artery incubation medium, while no trace of 6-keto-PGF1 alpha could be found in the placental medium. No conversion of AA to 6-keto-PGF1 alpha by placental microsomes was observed, even in the presence of antioxidants. The placenta possesses, in addition to the known 15-OH-PGDH and delta-13 reductase activities, a weak 9 OH PGDH which is specific for PGF2 alpha (and not PGI2 nor 6-keto-PGF1 alpha). GC-MS analysis showed that the expected metabolites of PGI2 through those three enzymes were not found in the placental medium, indicating that neither PGI2 synthesis nor metabolism could be demonstrated in the placenta.
D011452:15-Oxoprostaglandin 13-Reductase / Q000378:metabolism; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D015237:Dinoprost; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D010920:Placenta / Q000378:metabolism*; D010974:Platelet Aggregation; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D014469:Umbilical Arteries / Q000378:metabolism*
D000975:Antioxidants; D011453:Prostaglandins; D011460:Prostaglandins F; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; D015237:Dinoprost; D011464:Epoprostenol; D006911:Hydroxyprostaglandin Dehydrogenases; D011452:15-Oxoprostaglandin 13-Reductase; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase