Suppression of Intracellular Calcium Levels and Inhibition of Degranulation in RBL-2H3 Mast Cells by the Sesquiterpene Lactone Parthenolide

Pretreatment with parthenolide for 60 min inhibited the antigen-induced degranulation of RBL-2H3 mast cells; the IC(50) value being 4.5 +/- 0.4 mu M. The inhibition was not due to suppression of the phosphatidylinositol 3-kinase pathway because the antigen-induced phosphorylation of Akt was not inhibited by parthenolide. The antigen-induced increase in intracellular calcium levels was prevented by parthenolide, suggesting that parthenolide inhibited the antigen-induced degranulation by suppressing an increase in intracellular calcium levels. In support of this, parthenolide was found to prevent ionomycin-induced degranulation by inhibiting an increase in intracellular calcium levels. Therefore, parthenolide inhibits the degranulation of mast cells by preventing an increase in intracellular calcium levels.