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Uptake,transfer and metabolism of prostaglandin E2 in the isolated perfused human placental cotyledon
Institution:1. Heinrich-Heine-Universität Düsseldorf, Department of Rheumatology, Moorenstr. 5, 40225 Düsseldorf, Germany;2. Westfälische Wilhelms-Universität Münster, PharmaCampus, Institute of Pharmaceutical and Medicinal Chemistry, Corrensstr. 48, 48149 Münster, Germany;3. Westfälische Wilhelms-Universität Münster, Core Unit Proteomics, Interdisciplinary Center for Clinical Research, Röntgenstr. 21, 48149 Münster, Germany;4. Heinrich-Heine-Universität Düsseldorf, Department of Gynecology, Moorenstr. 5, 40225 Düsseldorf, Germany;1. Zebrafish Model Research Center for Human Diseases and Drug Screening in Western China, The College of Life Sciences, School of Medicine, Northwest University, Xi’an 710069, China;2. The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China;1. School of the Environment and Safety Engineering, Jiangsu University, 301 Xuefu Road Zhenjiang, 212013, China;2. School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road Zhenjiang, 212013, China;3. Yangzhou Tiancheng Water Treatment Equipment Engineering Co., LTD, Yangzhou, 225000, China;1. Department of Nephrology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan;2. Department of General Internal Medicine, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan
Abstract:(3H) PGE2 uptake and transfer in the isolated perfused human placental cotyledon was assessed by a ingle pass paired isotope dilution technique utilising (14C) sucrose as an extracellular marker. Metabolism of (3H) PGE2 was measured by analysing maternal and fetal effluents from perfused human placental cotyledons after bolus injection of (3H) PGE2 into ither the maternal or fetal sides. Maximal uptake of (3H) PGE2 was greater on the maternal (81 +/- 8%) than the fetal sides (42 +/- 12%) and showed saturation with increasing concentrations of PGE2 only on the fetal side with an apparent Km of 12 +/- 4.9 nmol/l and vmax of 1.5 +/- 0.2 pmol/min/g. Total recoveries of (3H) PGE2 were 84.6 +/- 11.8 % and 32.6 +/- 6.3 % of the injected dose after injection on the fetal and maternal sides respectively.Transferof (3H) PGE2 was the same in both directions being 6.4 +/- 1.2 % of the injected dose in the fetal-maternal direction and 5.8 +/- 2.7 % of the injected dose in the maternal-fetal direction. Metabolism was greater on the maternal side (35% of injected (3H) PGE2) thanthe fetalside(18% of injected (3H) PGE2) and was principally to the 13,14-dihydro-15-keto-PGE2 metabolite. Metabolism of (3H) PGE2 after passage across the placenta was the same in both directions and was of the order of approximately 60%.
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