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• W2057009043 abstract "This study investigated the mechanism underlying the inhibiting effect of (2R,3R)-2-(3′,4′-dihydroxybenzyl)-3-(3″,4″-dimethoxybenzyl) butyrolactone (PP-6), a lignan from Piper philippinum, on superoxide anion production induced by the chemotactic peptide formly-methionyl-leucyl-phenylalanine (fMLP) in human neutrophils. Human neutrophils were stimulated with fMLP (1 μM), PMA (100 nM) or leukotriene B4 (LTB4; 1 μM) and induced superoxide anion release. PP-6 specifically inhibited fMLP-induced superoxide anion production in a concentration-dependent manner with an IC50 value of 0.3 ± 0.1 μM. Intracellular signaling caused by fMLP, PMA or LTB4 were evaluated. PP-6 specifically inhibited fMLP-induced intracellular calcium mobilization and ERK (p42/p44), Akt and p38 phosphorylation. Moreover, PP-6 specifically inhibited fMLP-induced Mac-1 expression without affecting this caused by LTB4 or PMA. PP-6 did not increase cAMP level in human neutrophils. PP-6 did not inhibit superoxide anion production by NaF (20 mM), a direct activator of G-protein, the target of the inhibitory action of PP-6 appears to be a component of the signal transduction pathway upstream of G-protein. PP-6 inhibited FITC-fMLP binding to neutrophils in a concentration-dependent manner with an IC50 of 1.5 ± 0.2 μM. PP-6 did not bring a parallel shift in the concentration response of fMLP-induced superoxide anion. Additionally, the inhibiting effect of PP-6 on fMLP-induced superoxide anion was reversed when PP-6 was washed out. These experimental results suggest that PP-6 exerts non-competitive and reversible antagonistic effect on fMLP receptor." @default.
• W2057009043 created "2016-06-24" @default.
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• W2057009043 date "2008-02-01" @default.
• W2057009043 modified "2023-10-17" @default.
• W2057009043 title "(2R,3R)-2-(3′,4′-dihydroxybenzyl)-3-(3″,4″-dimethoxybenzyl)butyrolactone suppresses fMLP-induced superoxide production by inhibiting fMLP-receptor binding in human neutrophils" @default.
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• W2057009043 doi "https://doi.org/10.1016/j.bcp.2007.10.002" @default.
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