Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by xestobergsterol A from the Okinawan marine sponge Xestospongia bergquistia.
Histamine release from rat peritoneal mast cells induced by anti-IgE was essentially complete within 4-5 min. Xestobergsterol A and B, which are constituents of the Okinawan marine sponge Xestospongia bergquistia Fromont, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The IC50 values of xestobergsterol A and B for histamine release in mast cells activated by anti-IgE were 0.07 and 0.11 microM, respectively. Anti-IgE stimulated PI-PLC activity in a mast cell membrane preparation. Xestobergsterol A dose-dependently inhibited the generation of IP3 and membrane-bound PI-PLC activity. Moreover, xestobergsterol A inhibited Ca(2+)-mobilization from intracellular Ca(2+)-stores as well as histamine release in mast cells activated by anti-IgE. On the other hand, xestobergsterol B did not inhibit the membrane-bound and cytosolic PI-PLC activity, IP3 generation or the initial rise in [Ca2+]i in mast cells activated by anti-IgE. These results suggest that the mechanism of inhibition by xestobergsterol A of the initial rise in [Ca2+]i, of the generation of IP3, and of histamine release induced by anti-IgE, was through the inhibition of PI-PLC activity.
Takei
M
M
La Jolla Institute for Allergy and Immunology, California 92037.
Umeyama
A
A
Shoji
N
N
Arihara
S
S
Endo
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology; D002778:Cholestanones / Q000494:pharmacology*; D003063:Cnidaria / Q000737:chemistry*; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000378:metabolism
D002778:Cholestanones; C079917:xestobergsterol B; C079916:xestobergsterol A; D007073:Immunoglobulin E; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium