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 pr eformed mediators with IgE mediated stimulation, and these mediators a re considered to play an important role in allergic reactions. The coi ncident release of preformed mediators and AA metabolites suggests tha t AA metabolism is related to mast cell degranulation. To clarify the relationship between mast cell degranulation and AA metabolism, the ef fects of various AA cascade inhibitors on rat basophilic leukemia cell (RBL) mediator release induced by either anti-IgE or A23187 were exam ined. 5,8,11,14-eicosatetraynoic acid (ETYA) inhibited both PGD2 and L TC4/D4 generation, and partially inhibited serotonin release. Nordihyd roguaiaretic acid (NDGA) caused complete inhibition of LTC4/D4 generat ion, and partial inhibition of PGD2 generation and serotonin release. The cyclooxygenase inhibitor, indomethacin, and the specific 5-lipoxyg enase inhibitor, L-651,392 completely inhibited PGD2 and LTC4/D4 gener ation, respectively, without affecting release of other mediators. Bot h PGD2 and LTC4/D4 generation were abolished by the combination of ind omethacin and L-651,392, however, serotonin release remained intact. H PLC analysis showed that no shift to other AA metabolites occurred aft er the treatment with these inhibitors. Mepacrine, a phospholipase A2 inhibitor, completely inhibited PGD2 and LTC4/D4 generation, as well a s AArelease itself, without affecting serotonin release. Therefore, ne ither AA metabolism nor AA release is necessary for RBL degranulation.