MECHANISM OF INHIBITION OF IGE-DEPENDENT HISTAMINE-RELEASE FROM RAT MAST-CELLS BY PENASTEROL AND PENASTERONE

Penasterol and penasterone, constituents of the Okinawan marine sponge Penares incrustans, dose-dependently inhibited anti-IgE-induced hista mine release from rat mast cells. The concentrations of penasterol and penasterone required for 50% inhibition of anti-IgE-induced histamine release (IC50) were 0.5 and 1.5 mu M, respectively. Both compounds do se-dependently inhibited phospholipase A2 (PLA2) activity. Moreover, t hey inhibited anti-IgE-induced [H-3]arachidonic acid from rat mast cel ls. These results suggest that the mechanism of inhibition by these co mpounds of the histamine release induced by anti-IgE was through the i nhibition of PLA2.