Pharmacological studies of platelet-activating factor (PAF)-induced augmentation of response to histamine in guinea-pigs. 1994

T Sakurai, and S Yamaguchi, and T Iwama, and H Nagai
Department of Pharmacology, Gifu Pharmaceutical University, Japan.

An acute increase in airway response to histamine produced by platelet activating factor (PAF) was investigated pharmacologically in guinea-pigs. (1) The airway response to histamine (3 micrograms/kg) measured as pulmonary pressure was increased 8 min after injection of PAF at a dose of 25 ng/kg without affecting the numbers of leukocytes (macrophages, eosinophils, neutrophils and lymphocytes) in bronchoalveolar lavage fluid and airway capillary permeability. (2) To investigate the mechanism responsible for the PAF (25 ng/kg)-induced airway hyperresponsiveness to histamine, the effects of CV-3988 (a PAF-antagonist), ONO-1078 (a leukotriene (LT) antagonist), AA-861 (a 5-lipoxygenase inhibitor), indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane A2 (TXA2) synthetase inhibitor) and S-1452 (a TXA2 receptor antagonist) were examined. Simultaneously, to investigate the direct antagonistic effects of these drugs on PAF-induced response, the effects of above agents on PAF (150 ng/kg) induced bronchoconstriction were examined. CV-3988 completely inhibited both reactions, while ONO-1078 and AA-861 had no effect on both reactions. OKY-046, S-1452 and indomethacin inhibited PAF-induced bronchoconstriction more potently than PAF-induced airway hyperresponsiveness. These results indicate that inflammatory response is not involved in the onset of PAF-induced acute airway hyperreactivity. Results also suggest that TXA2 but not LT may play a role in the onset of this airway hyperreactivity and the role of TXA2 in hyperreactivity is less important than in PAF-induced bronchoconstriction.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008297 Male Males
D008689 Methacrylates Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group. Methacrylate
D010742 Phospholipid Ethers Phospholipids which have an alcohol moiety in ethereal linkage with a saturated or unsaturated aliphatic alcohol. They are usually derivatives of phosphoglycerols or phosphatidates. The other two alcohol groups of the glycerol backbone are usually in ester linkage. These compounds are widely distributed in animal tissues. Ether Phosphatidates,Ether Phospholipids,Glycerol Phosphate Ethers,Glycerophosphate Ethers,1-Alkyl-2-Acylphosphatidates,1 Alkyl 2 Acylphosphatidates,Ethers, Glycerol Phosphate,Ethers, Glycerophosphate,Ethers, Phospholipid,Phosphate Ethers, Glycerol,Phosphatidates, Ether,Phospholipids, Ether
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
D011312 Pressure A type of stress exerted uniformly in all directions. Its measure is the force exerted per unit area. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Pressures
D012137 Respiratory System The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. Respiratory Tract,Respiratory Systems,Respiratory Tracts,System, Respiratory,Tract, Respiratory
D012143 Respiratory Physiological Phenomena Physiological processes and properties of the RESPIRATORY SYSTEM as a whole or of any of its parts. Respiratory Physiologic Processes,Respiratory Physiological Processes,Respiratory Physiology,Physiology, Respiratory,Pulmonary Physiological Phenomena,Pulmonary Physiological Phenomenon,Pulmonary Physiological Process,Pulmonary Physiological Processes,Respiratory Physiological Concepts,Respiratory Physiological Phenomenon,Respiratory Physiological Process,Concept, Respiratory Physiological,Concepts, Respiratory Physiological,Phenomena, Pulmonary Physiological,Phenomena, Respiratory Physiological,Phenomenas, Pulmonary Physiological,Phenomenas, Respiratory Physiological,Phenomenon, Pulmonary Physiological,Phenomenon, Respiratory Physiological,Phenomenons, Pulmonary Physiological,Phenomenons, Respiratory Physiological,Physiologic Processes, Respiratory,Physiological Concept, Respiratory,Physiological Concepts, Respiratory,Physiological Phenomena, Pulmonary,Physiological Phenomena, Respiratory,Physiological Phenomenas, Pulmonary,Physiological Phenomenas, Respiratory,Physiological Phenomenon, Pulmonary,Physiological Phenomenon, Respiratory,Physiological Phenomenons, Pulmonary,Physiological Phenomenons, Respiratory,Physiological Process, Pulmonary,Physiological Process, Respiratory,Physiological Processes, Pulmonary,Physiological Processes, Respiratory,Process, Pulmonary Physiological,Process, Respiratory Physiological,Processes, Pulmonary Physiological,Pulmonary Physiological Phenomenas,Pulmonary Physiological Phenomenons,Respiratory Physiological Concept,Respiratory Physiological Phenomenas,Respiratory Physiological Phenomenons
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

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