Effects of inhibitors of arachidonic acid metabolism on serotonin release from rat basophilic leukemia cells

Mast cells can release arachidonic acid (AA) metabolites as well as preformed mediators with IgE mediated stimulation, and these mediators are considered to play an important role in allergic reactions. The coincident release of preformed mediators and AA metabolites suggests that AA metabolism is related to mast cell degranulation. To clarify the relationship between mast cell degranulation and AA metabolism, the effects of various AA cascade inhibitors on rat basophilic leukemia cell (RBL) mediator release induced by either anti-IgE or A23187 were examined. 5,8,11,14-eicosatetraynoic acid (ETYA) inhibited both PGD₂ and LTC₄/D₄ generation, and partially inhibited serotonin release. Nordihydroguaiaretic acid (NDGA) caused complete inhibition of LTC₄/D₄ generation, and partial inhibition of PGD₂ generation and serotonin release. The cyclooxygenase inhibitor, indomethacin, and the specific 5-lipoxygenase inhibitor, L-651,392 completely inhibited PGD₂ and LTC₄/D₄ generation, respectively, without affecting release of other mediators. Both PGD₂ and LTC₄/D₄ generation were abolished by the combination of indomethacin and L-651,392, however, serotonin release remained intact. HPLC analysis showed that no shift to other AA metabolites occurred after the treatment with these inhibitors. Mepacrine, a phospholipase A₂ inhibitor, completely inhibited PGD₂ and LTC₄/D₄ generation, as well as AArelease itself, without affecting serotonin release. Therefore, neither AA metabolism nor AA release is necessary for RBL degranulation.