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• W2053907246 abstract "The fungal metabolite, wortmannin, has recently been shown to inhibit fMet‐Leu‐Phe‐stimulated superoxide production and phospholipase D (PLD) activation in the human neutrophil. We have found that a close structural analogue of wortmannin, demethoxyviridin, has a similar inhibitory profile but in addition blocks phosphatidylinositol 4,5‐bisphosphate‐specific phospholipase C and hence inositol 1,4,5‐trisphosphate (IP 3 ) formation. Inhibition of fMet‐Leu‐Phe‐stimulated PLD by demethoxyviridin was characteristically non‐competitive (IC 50 = 31 ± 10 n m ). Inhibition of fMet‐Leu‐Phe‐stimulated IP 3 formation required concentrations almost 10 times higher (IC 50 = 250 ± 130 n m ). Surprisingly, demethoxyviridin only inhibited fMet‐Leu‐Phe‐induced intracellular calcium mobilization at concentrations 100 times greater than those needed to block IP 3 formation. Demethoxyviridin also inhibited PLD activation induced by sodium fluoride or phorbol myristate acetate (PMA) but the concentrations required were 100 times those needed to block fMet‐Leu‐Phe‐stimulated PLD. These observations support the contention that PLD plays an important role in signal transduction in the human neutrophil and indicate that wortmannin and demethoxyviridin inhibit PLD activation at a common step in the signalling pathway. Furthermore, these results suggest that demethoxyviridin may block the interaction between the chemotactic peptide receptor and a GTP‐binding protein that is intimately involved in PLD activation." @default.
• W2053907246 created "2016-06-24" @default.
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• W2053907246 date "1991-05-01" @default.
• W2053907246 modified "2023-10-17" @default.
• W2053907246 title "Demethoxyviridin and wortmannin block phospholipase C and D activation in the human neutrophil" @default.
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• W2053907246 doi "https://doi.org/10.1111/j.1476-5381.1991.tb12330.x" @default.
• W2053907246 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1908105" @default.
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