title: Effect of exogenous arachidonic acid and enzyme inhibitors on placental prostanoid production.
abstract: Prostanoids play an important role throughout pregnancy and during the initiation and progress of labor. The human placenta, at term, produces large quantities of prostanoids, yet little is known of the rate-limiting steps regulating their biosynthesis. In these studies, the effect of exogenous arachidonic acid and of enzyme inhibitors on the release of placental prostanoids was investigated. Basal prostaglandin E (PGE), prostaglandin F (PGF), thromboxane (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) increased from the fifth hour in culture, yet the increased PGF release did not result in further 13,14-dihydro-15-keto-PGF2 alpha (PGFM) production. Addition of varying doses of arachidonic acid (0.2-10 micrograms/ml) had no significant effect on PGFM, TxB2 or 6-keto-PGF1 alpha, although the endogenous arachidonate was similar to or much less than the doses studied. Only at the 10 micrograms/ml dose was a delayed increase of PGE and PGF observed. Incubation with indomethacin resulted in an immediate inhibition of PGE, PGF, TxB2 and 6-keto-PGF1 alpha, with a delayed inhibition of PGFM. The phospholipase A2 inhibitor, quinacrine (10 microM), had no significant effect on PGE, PGFM, TxB2 or 6-keto-PGF1 alpha. PGF was inhibited within the first hour of quinacrine exposure, but no significant inhibition was observed thereafter. Ca2+ chelator, EDTA, effected an inhibition of only 6-keto-PGF1 alpha. Nordihydroguaiaretic acid, a leukotriene inhibitor, reduced PGE release as well as 6-keto-PGF1 alpha. These data demonstrate the high biosynthetic competence of the human term placenta to produce prostanoids. This capacity does not appear to be rate-limited by arachidonic acid availability. However, the metabolism of PGF to PGFM appears to be saturated. In addition, the production of placenta prostacyclin may be affected by Ca2+ levels, as chelating agent inhibited the release of 6-keto-PGF1 alpha.
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Health Science Center, San Antonio 78284-7836.
authors.forename: I S
authors.initials: IS
authors.lastname: Kang
authors.forename: T M
authors.initials: TM
authors.lastname: Siler-Khodr
mesh_terms: D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D015289:Leukotrienes / Q000502:physiology; D009637:Masoprocol / Q000494:pharmacology; D010740:Phospholipases / Q000502:physiology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011796:Quinacrine / Q000494:pharmacology; D011863:Radioimmunoassay; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D015289:Leukotrienes; D011453:Prostaglandins; D016718:Arachidonic Acid; D009637:Masoprocol; D004492:Edetic Acid; D010740:Phospholipases; D011796:Quinacrine; D002118:Calcium