title: Effect of azelastine on airway hyperresponsiveness mediated by stimulated macrophages.
abstract: The effect of the anti-allergic drug azelastine, 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4-yl)-1-(2H)-phth alazione), on airway hyperresponsiveness induced by immunologically stimulated pulmonary alveolar macrophages was investigated in canine bronchial segments under isometric conditions in vitro. Macrophages stimulated with anti-dinitrophenyl immunoglobulin E (IgE) antibody and dinitrophenyl-human serum albumin potentiated the contractile responses to electrical field stimulation at all frequencies, an effect that was abolished by azelastine (3 x 10(-5) M). In contrast, azelastine had no effect on the potentiation of the contractile responses to electrical stimulation by U46619, a thromboxane A2 mimetic. The IgE-mediated release of thromboxane A2 from macrophages was inhibited by azelastine in a concentration-dependent fashion, the maximal decrease and the concentration required to produce a half-maximal effect being 84 +/- 6% (P < 0.001) and 16 microM, respectively. These results suggest that azelastine may attenuate macrophage-induced parasympathetic airway hyperresponsiveness through an inhibition of the release of thromboxane A2.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical College, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Tamaoki
authors.forename: H
authors.initials: H
authors.lastname: Takemura
authors.forename: E
authors.initials: E
authors.lastname: Tagaya
authors.forename: A
authors.initials: A
authors.lastname: Sakai
authors.forename: I
authors.initials: I
authors.lastname: Yamawaki
authors.forename: K
authors.initials: K
authors.lastname: Konno
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012709:Serum Albumin / Q000276:immunology; D009435:Synaptic Transmission / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011450:Prostaglandin Endoperoxides, Synthetic; D012709:Serum Albumin; D014662:Vasoconstrictor Agents; D007073:Immunoglobulin E; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C020976:azelastine