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 µM. 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.
Hong
Jangja
J
Laboratory of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
Aoyama
Suzue
S
Hirasawa
Noriyasu
N
Zee
Okpyo
O
Ishihara
Kenji
K
Hashida
Chika
C
Kimura
Michio
M
Seyama
Toshio
T
Ohuchi
Kazuo
K
D000818:Animals; D000941:Antigens / Q000009:adverse effects; D002118:Calcium / Q000378:metabolism*; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D007155:Immunologic Factors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015759:Ionomycin; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D031203:Tanacetum / Q000737:chemistry*
D000941:Antigens; D007155:Immunologic Factors; D010936:Plant Extracts; D012717:Sesquiterpenes; C002669:parthenolide; D015759:Ionomycin; D002118:Calcium