Y. Igarashi et al., EFFECTS OF INHIBITORS OF ARACHIDONIC-ACID METABOLISM ON SEROTONIN RELEASE FROM RAT BASOPHILIC LEUKEMIA-CELLS, Immunopharmacology, 25(2), 1993, pp. 131-144
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.