EFFECTS OF 3 DIFFERENT CA2-ATPASE INHIBITORS ON CA2+ RESPONSE AND LEUKOTRIENE RELEASE IN RBL-2H3 CELLS()

The effects of three Ca2+-ATPase inhibitors, thapsigargin (TG), cyclop iazonic acid (CPA), and 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), o n the Ca2+ response, degranulation, and leukotriene C-4 (LTC(4)) relea se in RBL-2H3 cells were investigated. All three compounds elevated th e intracellular free Ca2+ concentration ([Ca2+](i)), and caused degran ulation in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator. The dose-dependency of each compound in the Ca2+ response was in good agreement with that in degranulation. T G and CPA also caused the release of LTC(4) in a dose-dependent manner , and this effect was unaffected by TPA or calphostin C, a selective P KC inhibitor. DTBHQ, however, did not induce LTC(4) release, and rathe r inhibited the antigen-induced release of LTC(4). These results sugge st [1] that both degranulation and LTC(4) release caused by these comp ounds are dependent on their [Ca2+](i) increasing effect, [2] that deg ranulation and LTC(4) release are mediated via independent pathways fo llowing the Ca2+ response, and [3] that DTBHQ additionally prevents th e synthesis of LTC(4) possibly by inhibition of 5-lipoxygenase.