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Overnight (10–16 h) incubation of retinoic acid (RA), a derivative of vitamin A, specifically induced LTC4 synthase activity (5 to 10-fold), but not LTA4 hydrolase activity in the lysate of rat basophilic leukemia-1 (RBL-1) cells. A time course study revealed that the increase of LTC4 synthase activity was time dependent and that the peak value was obtained after a 24-hour incubation with RA. The induction of enzyme activity was specifically localized to the microsomal fraction. Glutathione (GSH) S-transferase activity measured by using the same cell lysate as an enzyme source and 1-chloro-2,4-dinitrobenzene (DNCB) as a substrate was not influenced by RA treatment, indicating that the induction by RA is specific for membrane-bound LTC4 synthase. The induction of LTC4 synthase may be an important regulatory mechanism of peptide-LT synthesis in allergy and inflammatory diseases.

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We investigated the inhibitory action of FK506 (0.0005-5 µg/ml) on the metabolism of arachidonate 5-lipoxygenase in rat basophilic leukemia-1 cells. Cells were stimulated with A23187 (10^-5 mol/l) for 15 min in the absence or presence of various concentrations of FK506. Arachidonate 5-lipoxygenase metabolites, peptide leukotrienes (LTs), leukotriene B₄ (LTB₄) and 5-hydroxyeicosatetraenoic acid (5-HETE) were measured by high-performance liquid chromatography. FK506 inhibited A23187-stim-ulated production of peptide LTs, LTB4 and 5-HETE in intact cells by up to 77, 73 and 60%, respectively. Phospholipase A₂ activity, measured by the release of ³H-achidonic acid (AA), was not significantly inhibited by FK506. The synthesis of peptide LTs and LTB4 was not inhibited by FK506 when leukotriene A₄-free acid was added to the culture medium. The synthesis of peptide LTs, LTB4 and 5-HETE was not affected by FK506 in a cell lysate study using AA as the subtrate. These results indicate that FK506 inhibits the production of peptide LTs, LTB₄ and 5-HETE by inhibiting 5-lipoxygenase activity in intact cells. The inhibition is not a direct action on 5-lipoxygenase but results from the activating processes of this enzyme.