We investigated the inhibitory action of FK506 (0.0005-5 mu g/ml) on t
he metabolism of arachidonate 5-lipoxygenase in rat basophilic leukemi
a-1 cells. Cells were stimulated with A23187 (10(-5) mol/1) for 15 min
in the absence or presence of various concentrations of FK506. Arachi
donate 5-lipoxygenase metabolites, peptide leukotrienes (LTs), leukotr
iene Bq (LTB(4)) and 5-hydroxyeicosatetraenoic acid (5-HETE) were meas
ured by high-performance liquid chromatography. FK506 inhibited A23187
-stimulated production of peptide LTs, LTB(4) and 5-HETE in intact cel
ls by up to 77, 73 and 60%, respectively. Phospholipase Az activity, m
easured by the release of H-3-arachidonic acid (AA), was not significa
ntly inhibited by FK506. The synthesis of peptide LTs and LTB(4) was n
ot inhibited by FK506 when leukotriene A(4)-free acid was added to the
culture medium. The synthesis of peptide LTs, LTB(4) and 5-HETE was n
ot affected by FK506 in a eel lysate study using AA as the subtrate. T
hese results indicate that FK506 inhibits the production of peptide LT
s, LTB(4) and 5-HETE by inhibiting 5-lipoxygenase activity in intact c
ells. The inhibition is not a direct action on 5-lipoxygenase but resu
lts from the activating processes of this enzyme.