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Role of lipoxygenase metabolites in platelet-activating factor- and antigen-induced bronchial hyperresponsiveness and eosinophil infiltration. 1995

E A Seeds, and S Kilfeather, and S Okiji, and T S Schoupe, and D Donigi-Gale, and C P Page
Department of Pharmacology, King's College, University of London, UK.

The effect of a novel leuktriene B4 receptor antagonist N-[5[[8-(1-hydroxy-2- phenyl)ethyl]dibenzofuran-2yl]5-hydroxypentanoyl]pyrrolidine (PF 10042) has been evaluated in comparison with 2-[3(1-hydroxyhexyl)phenoxymethyl]quinoline hydrochloride (PF 5901), a specific inhibitor of the 5-lipoxygenase pathway of arachidonic acid metabolism, against platelet activating factor (PAF) and allergen induced bronchial hyperresponsiveness and pulmonary eosinophil infiltration in the guinea pig. PF 10042 significantly displaced radiolabelled [3H]leukotriene B4 from binding sites on human neutrophils with an EC50 of 3 muM. PF 10042 (100 mg/kg, i.p.) significantly inhibited PAF and allergen induced bronchial hyperresponsiveness without reducing the concomitant eosinophil infiltration, whereas PF 5901 (100 mg/kg, p.o.) significantly inhibited both PAF and allergen induced bronchial hyperresponsiveness and eosinophil infiltration. We suggest from these results that PAF and allergen induced bronchial hyperresponsiveness may be secondary to the release of leukotriene B4, but this lipoxygenase metabolite does not contribute significantly to the observed eosinophil infiltration.

UI MeSH Term Description Entries
D008084 Lipoxygenase An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Lipoxidase,Linoleate-Oxygen Oxidoreductase,Lipoxygenase-1,Lipoxygenase-2,Linoleate Oxygen Oxidoreductase,Lipoxygenase 1,Lipoxygenase 2,Oxidoreductase, Linoleate-Oxygen
D008297 Male Males
D010047 Ovalbumin An albumin obtained from the white of eggs. It is a member of the serpin superfamily. Serpin B14
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D011657 Pulmonary Eosinophilia A condition characterized by infiltration of the lung with EOSINOPHILS due to inflammation or other disease processes. Major eosinophilic lung diseases are the eosinophilic pneumonias caused by infections, allergens, or toxic agents. Eosinophilia, Pulmonary,Eosinophilic Pneumonia,Loeffler Syndrome,Pneumonia, Eosinophilic,Eosinophilias, Pulmonary,Pulmonary Eosinophilias,Simple Pulmonary Eosinophilia,Tropical Eosinophilic Pneumonia,Eosinophilic Pneumonia, Tropical,Eosinophilic Pneumonias,Eosinophilic Pneumonias, Tropical,Pneumonias, Eosinophilic,Pulmonary Eosinophilia, Simple,Simple Pulmonary Eosinophilias,Syndrome, Loeffler,Tropical Eosinophilic Pneumonias
D011804 Quinolines
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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