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• W2056534485 abstract "We evaluated the pharmacological effect of statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) on mast cell degranulation in RBL-2H3 cells. A hydrophilic statin (pravastatin) did not inhibit degranulation induced by dinitrophenol-human serum albumin (DNP-HSA); in contrast, lipophilic statins (simvastatin, fluvastatin and atorvastatin) inhibited DNP-HSA-induced degranulation in that order. The inhibitory effects were completely attenuated by simultaneous treatment with 100-1000 microM mevalonic acid for 4 h. We used fluvastatin to clarify the mechanism of the statin-mediated inhibitory action of mast cell degranulation. Fluvastatin (3 microM) had no effect on Ca(2+) release from the endoplasmic reticulum or Ca(2+) influx in the DNP-HSA- or thapsigargin-stimulated cells. Fluvastatin treatment also had no effect on the total granule content of the cell or sensitivity to DNP-HSA and IgE. Fluvastatin (3 microM, 24 h treatment) also failed to affect the morphology, proliferation, and viability of RBL-2H3 cells. Geranylgeranyl transferase inhibitor, GGTI-286 (20 microM), but not farnesyl transferase inhibitor, FPTIII (20 microM), inhibited the DNP-HSA-induced degranulation. The GGTI-286-induced inhibitory action was not associated with a decrease in the cytoplasmic Ca(2+) level. In conclusion, fluvastatin at a lower concentration range inhibited DNP-HSA-induced degranulation without affecting the cytoplasmic Ca(2+) response and also without changing the amount of granule content and proliferation of the mast cells. The statin-induced inhibitory action may be mediated by the suppression of geranylgeranyl transferase via the depletion of intracellular mevalonic acid." @default.
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• W2056534485 date "2009-01-01" @default.
• W2056534485 modified "2023-10-03" @default.
• W2056534485 title "Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level" @default.
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• W2056534485 doi "https://doi.org/10.1016/j.ejphar.2008.11.040" @default.
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