We previously reported that a
hydroquinone-type
antioxidant, 2,5-di(tert-butyl)-1,4-hydroquinone (
DTBHQ), increases intracellular free Ca2+ concentration ([Ca2+]i), causes degranulation together with a
protein kinase C activator,
phorbol 12-myristate 13-acetate (TPA), and increases
antigen-induced degranulation in rat basophilic
leukemia (RBL-2H3) cells. In this study, the effects of five-
hydroquinone-type and phenolic
antioxidants (2,5-di(tert-amyl)-1,4-
hydroquinone [DTAHQ], 2-tert-butyl-1,4-
hydroquinone [
MTBHQ], 3,5-di(tert-butyl)-4-hydroxytoluene [
BHT], 3,5-di(tert-butyl)-4-hydroxyanisole [DTBHA], and 3-tert-butyl-4-hydroxyanisole [MTBHA]) on [ca2+]i and degranulation (
beta-hexosaminidase release) were examined and compared with that of
DTBHQ. DTAHQ (> or = 3 microM) showed effects similar to those of
DTBHQ (10 microM) on [Ca2+]i elevation, induction of degranulation with TPA, and increase of
antigen-induced degranulation.
BHT (50 microM) and DTBHA (50 microM) caused [Ca2+]i elevation and increased degranulation in the presence of TPA or
antigen, but their effects were less than those of
DTBHQ and DTAHQ.
MTBHQ and MTBHA had no effect on [Ca2+]i and degranulation, even at 50 microM. The degree of Ca2+ response caused by the compounds correlated well with the increase in degranulation, but not with their
antioxidant activity estimated with the first oxidation potential. From these results, it is suggested that the increasing effects of six
antioxidants on degranulation in the presence of TPA or
antigen were dependent on [Ca2+]i increase caused by the compounds, probably through their ability to inhibit endoplasmic reticulum Ca2+-
ATPase.