title: A 5-lipoxygenase inhibitor, FR110302, suppresses airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles in rats.
abstract: To study the role of chemical mediators in airway hyperresponsiveness and simultaneous eosinophilia, we examined effects of a potent 5-lipoxygenase inhibitor FR110302 and those of prednisolone, indomethacin, platelet-activating factor (PAF) antagonist (RP-59227) and leukotriene C4 (LTC4) antagonist (ONO-1078) on airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles. Sephadex G200 particles (2.5 mg/kg) were injected intravenously to rats and 3 days later the airway hyperresponsiveness to acetylcholine (ACh) and the eosinophilia in the bronchoalveolar lavage (BAL) fluids were observed. FR110302 (10 mg/kg b.i.d.p.o.) significantly suppressed both of these indicators of asthma. The amounts of immunoreactive LTB4,C4 (i-LTB4, C4) in the BAL fluid were measured by radioimmunoassay. The amounts of i-LTB4,C4 in the FR110302-treated rats were significantly less compared with that in the Sephadex-injected controls. Prednisolone completely inhibited the airway hyperresponsiveness. PAF antagonist and LTC4 antagonist partially inhibited the airway hyperresponsiveness, and indomethacin had no effect. The results indicate that 5-lipoxygenase products play important roles in the Sephadex-induced airway hyperresponsiveness and lung eosinophilia in rats.
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd. Tsukuba Research Laboratories, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: N
authors.initials: N
authors.lastname: Inamura
authors.forename: K
authors.initials: K
authors.lastname: Nakahara
authors.forename: A
authors.initials: A
authors.lastname: Nagayoshi
authors.forename: T
authors.initials: T
authors.lastname: Isono
authors.forename: K
authors.initials: K
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Oku
authors.forename: Y
authors.initials: Y
authors.lastname: Notsu
authors.forename: M
authors.initials: M
authors.lastname: Kohsaka
authors.forename: T
authors.initials: T
authors.lastname: Ono
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002867:Chromones / Q000494:pharmacology; D003911:Dextrans; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D009284:Naphthols / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011239:Prednisolone / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000517:prevention & control*; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D002867:Chromones; D003911:Dextrans; D016859:Lipoxygenase Inhibitors; D009284:Naphthols; D010972:Platelet Activating Factor; D011725:Pyridines; D011804:Quinolines; D013189:SRS-A; D013844:Thiazoles; C065022:RP 59227; C074243:FR 110302; D007975:Leukotriene B4; C025614:sephadex; D011239:Prednisolone; D000109:Acetylcholine; C047681:pranlukast; D007213:Indomethacin