Inhibition of leukotriene synthesis by terfenadine in vitro.
To determine the inhibitory mechanisms of terfenadine on the synthesis of leukotriene C4 (LTC4), an important mediator in allergic diseases, we evaluated the action of terfenadine on the IgE-dependent production of LTC4 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 LTC4 released into the medium was measured by performing a specific radio immunoassay. Terfenadine inhibited the synthesis of LTC4 to 67.2% at a concentration of 5 microg/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 A2 and 5-LO by blocking the influx of intracellular calcium ion that was initiated by IgE-related stimulation.
Hamasaki
Y
Y
Saga Medical School, Department of Paediatrics, Nebeshima, Japan.
Kita
M
M
Hayasaki
R
R
Zaitu
M
M
Muro
E
E
Yamamoto
S
S
Kobayashi
I
I
Matsuo
M
M
Ichimaru
T
T
Miyazaki
S
S
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D017572:Leukotriene A4 / Q000378:metabolism; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis*; D013379:Substrate Specificity; D016593:Terfenadine / Q000494:pharmacology*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018926:Anti-Allergic Agents; D000900:Anti-Bacterial Agents; D000888:Antibodies, Anti-Idiotypic; D017572:Leukotriene A4; D020024:Leukotriene Antagonists; D015289:Leukotrienes; C026408:anti-IgE antibodies; D014316:Tritium; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D007073:Immunoglobulin E; D000001:Calcimycin; D016593:Terfenadine; D002118:Calcium