Effects of ZCR-2060 on allergic airway inflammation and cell activation in guinea-pigs.
The effects of 2-(2-(4-(diphenylmethyl)-1-piperadinyl) ethoxy) benzoic acid malate (ZCR-2060) on allergic airway inflammation and inflammatory cell activation in guinea-pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively-sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen-induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR-2060 (1 mg kg-1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR-2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in-vitro was studied. ZCR-2060 (10(-6)-10(-4) M) inhibited the platelet-activating factor (PAF)-induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B4-induced chemotaxis of eosinophils and the formyl-Met-Leu-Phe-induced chemotaxis of neutrophils. PAF-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR-2060 (10(-6)-10(-4) M). However, ZCR-2060 did not affect phorbol myristate acetate-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR-2060 inhibits allergic airway inflammation, and PAF-induced inflammatory cell activation in guinea-pigs. ZCR-2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.
Abe
T
T
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Yoshida
K
K
Omata
T
T
Segawa
Y
Y
Matsuda
K
K
Nagai
H
H
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology*; D007975:Leukotriene B4 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001565:Benzoates; D010880:Piperidines; D010972:Platelet Activating Factor; C091433:ZCR 2060; D013481:Superoxides; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate