title: Inhibition of leukotriene synthesis by terfenadine in vitro.
abstract: 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.
authors.affiliation: Saga Medical School, Department of Paediatrics, Nebeshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: M
authors.initials: M
authors.lastname: Kita
authors.forename: R
authors.initials: R
authors.lastname: Hayasaki
authors.forename: M
authors.initials: M
authors.lastname: Zaitu
authors.forename: E
authors.initials: E
authors.lastname: Muro
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.forename: T
authors.initials: T
authors.lastname: Ichimaru
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
mesh_terms: 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
chemical_list: 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