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• W2095860695 abstract "Circulating levels of platelet-activating factor (PAF) are high in the fetus, and PAF is active in maintaining high PVR in fetal hypoxia (Ibe BO, Hibler S, Raj J. J Appl Physiol 85: 1079–1085, 1998). PAF synthesis by fetal pulmonary vascular smooth muscle cells (PVSMC) is high in hypoxia, but how oxygen tension affects PAF receptor (PAF-r) binding in PVSMC is not known. We studied the effect of oxygen tension on PAF-r binding and signaling in fetal PVSMC. PAF binding was saturable. PAF-r density (B max : fmol/10 6 cells; means ± SE, n = 6), 25.2 ± 0.77 during hypoxia (Po 2 <40 Torr), was higher than 13.9 ± 0.44 during normoxia (Po 2 ∼100 Torr). K d was twofold lower in hypoxia than normoxia. PAF-r protein expression, 35–40% greater in hypoxia, was inhibited by cycloheximide, a protein synthesis inhibitor, suggesting translational regulation. IP 3 release, an index of PAF-r-mediated cell signaling, was greater in hypoxia (EC 50 : hypoxia, 2.94 ± 0.61; normoxia, 5.85 ± 0.51 nM). Exogenous PAF induced 50–90% greater intracellular calcium flux in cells during hypoxia, indicating hypoxia augments PAF-r-mediated cell signaling. PAF-r phosphorylation, with or without 5 nM PAF, was 40% greater in hypoxia. These data show 1) hypoxia upregulates PAF-r binding, PAF-r phosphorylation, and PAF-r-mediated intracellular signaling, evidenced by augmented IP 3 production and intracellular Ca 2+ flux; and 2) hypoxia-induced PAF-r phosphorylation results in activation of PAF-r-mediated signal transduction. The data suggest the fetal hypoxic environment facilitates PAF-r binding and signaling, thereby promoting PAF-mediated pulmonary vasoconstriction and maintenance of high PVR in utero." @default.
• W2095860695 created "2016-06-24" @default.
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• W2095860695 date "2005-05-01" @default.
• W2095860695 modified "2023-10-15" @default.
• W2095860695 title "Oxygen-dependent PAF receptor binding and intracellular signaling in ovine fetal pulmonary vascular smooth muscle" @default.
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• W2095860695 doi "https://doi.org/10.1152/ajplung.00341.2004" @default.
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