Effect of PGE₂ and its analogs on FcϵRI-dependent and -independent eicosanoid generation. (A) Dose response (left panel) for the suppressive effect of PGE₂ on eicosanoid formation by IL-4-primed, sensitized hMCs stimulated for 30 minutes with anti-IgE. Data in second experiment were similar. Effect of 10 μM PGE₂ (right panel) or buffer control. Data are means ± SEM over 5 experiments, expressed as percent of control (quantities generated in the presence of buffer alone). (B) Dose-dependent effects of EP₂ receptor-selective antagonist AE1-259-01 and EP₃ receptor-selective agonist AE-248 on FcϵRI-mediated PGD₂ generation (top panel). Results from a second experiment were similar. Effect of 10 μM AE1-259, AE-248, and the EP₄ receptor-selective agonist AE-329 (10 μM each) on FcϵRI-mediated generation of LTC₄ (middle panel, as measured by an ELISA for cysLTs) and PGD₂ (bottom panel). Values are means ± SEM from 4 experiments, normalized to percentage of control (cells stimulated in the presence of DMSO). (C) Induction of eicosanoid generation directly in response to PGE₂ and its analogs. Cells were stimulated for 30 minutes with PGE₂ or the indicated receptor-selective analogs, or with buffer control (DMSO), with or without pretreatment with H89 for 30 minutes. Dose-dependent effect of AE-248 and AE1-259-01 on PGD₂ generation by primed hMCs without FcϵRI cross-linkage (top panel). Data in a second experiment were similar. The effects of 10 μM PGE₂ and selective agonists in the presence or absence of the PKA inhibitor H89 (10 μM) are displayed for cys LTs (middle panel) and PGD₂ (bottom panel). Data in the latter 2 panels are means ± SEM from 3 experiments. ^*Significantly different from control.