N. Hirasawa et al., INHIBITION OF HISTAMINE-RELEASE FROM RBL-2H3 CELLS BY PROTEIN-SYNTHESIS INHIBITORS, International archives of allergy and immunology, 103(3), 1994, pp. 266-273
Effects of cycloheximide, an inhibitor of protein synthesis, on histam
ine release from RBL-2H3 cells were examined. RBL-2H3 cells sensitized
by rat antiserum to ascaris extract were challenged by the antigen, a
nd histamine release during a period of 30 min was measured. Pretreatm
ent with cycloheximide (1 mu g/ml) for 1 h significantly inhibited the
antigen-induced histamine release (36% inhibition). The cycloheximide
-induced inhibition of histamine release was abolished when the cells
were further incubated in the absence of cycloheximide for 2 h. Pretre
atment with puromycin (3 and 10 mu g/ml), an inhibitor of protein synt
hesis, or actinomycin D (0.1-1 mu g/ml), an inhibitor of DNA-dependent
RNA synthesis, also inhibited the antigen-induced histamine release i
n a concentration-dependent manner. Both ionomycin- and thapsigargin-i
nduced histamine release were also inhibited by pretreatment with cycl
oheximide. Measurement of intracellular Ca2+ levels using quin 2 revea
led that cycloheximide inhibits the increase in Ca2+ levels induced by
the antigen, ionomycin or thapsigargin. These results suggest that hi
stamine release induced by the antigen, ionomycin and thapsigargin in
RBL-2H3 cells is mediated by protein(s) which is newly synthesized and
inactivated rapidly, and the newly synthesized protein(s) is involved
in the increase of intracellular Ca2+ levels induced by these stimula
nts.