Inhibition of leukotriene synthesis by terfenadine in vitro.
1998
Abstract To determine the inhibitory mechanisms of terfenadine on the synthesis of leukotriene C 4 (LTC 4 ), an important mediator in allergic diseases, we evaluated the action of terfenadine on the IgE-dependent production of LTC 4 in rat basophilic leukaemia 2H3 cells. Rat IgE-loaded cells were stimulated with anti-IgE in the presence or absence of various concentrations of terfenadine and the level of LTC 4 released into the medium was measured by performing a specific radio immunoassay. Terfenadine inhibited the synthesis of LTC 4 to 67.2% at a concentration of 5 μg/ml. LT synthesis was directly suppressed by inhibition of 5-lipoxygenase (5-LO) through calcium ion-independent mechanisms, and was also possibly suppressed by inhibition of cytosolic phospholipase A 2 and 5-LO by blocking the influx of intracellular calcium ion that was initiated by IgE-related stimulation.
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