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Comparison of the anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung. 1993

C J Whelan, and M Johnson, and C J Vardey
Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd., Ware, Herts.

1. We have compared some anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung. 2. Intradermal formoterol (1 x 10(-10) to 1 x 10(-8) mol/site), salbutamol (1 x 10(-8) and 1 x 10(-7) mol/site) and salmeterol (1 x 10(-8) and 1 x 10(-7) mol/site) inhibited bradykinin-induced plasma protein extravasation (PPE) in guinea-pig skin. A maximally effective dose of formoterol (1 x 10(-9) mol/site) and salbutamol (1 x 10(-8) mol/site) inhibited PPE in guinea-pig skin for 2-4 h and 1-2 h respectively, whereas salmeterol (1 x 10(-8) mol/site) was effective for > 6 h. 3. Inhaled formoterol (nebuliser concentration 0.1 to 100 micrograms ml-1 inhibited histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, with significant inhibition being observed at 10 and 100 micrograms ml-1. Formoterol (100 micrograms ml-1) inhibited PPE in guinea-pig lung for 2-4 h, a duration of action intermediate between that previously obtained for salbutamol (1 h) and salmeterol (> 6 h). 4. Formoterol, like salbutamol, had no effect on neutrophil accumulation or granulocyte-dependent PPE (zymosan-induced) in guinea-pig skin. Formoterol inhibited neutrophil accumulation (lipopolysaccharide-induced) in guinea-pig lung but at doses greater than those required to inhibit granulocyte-independent PPE (histamine-induced). In contrast, salmeterol inhibited neutrophil accumulation and granulocyte-dependent PPE in guinea-pig skin and inhibited neutrophil accumulation in guinea-pig lung at doses which inhibit granulocyte-independent PPE. 5. Inhaled formoterol (nebuliser concentration 100 microg ml-1) and salmeterol (100 microg ml-1) both inhibited PAF-induced eosinophil accumulation in guinea-pig lung. However, unlike salmeterol, this effect of formoterol was observed only at suprabronchodilator doses.6. We conclude that to inhibit neutrophil accumulation, at doses which inhibit granulocyte-independent PPE, agonists acting at beta-adrenoceptors on vascular endothelium require a duration of action greater than that of salbutamol and formoterol. However, we speculate that the mechanism of inhibition of eosinophil accumulation in guinea-pig lung by beta2-adrenoceptor agonists may involve an action on beta2-adrenoceptors on a cell type other than the endothelial cell.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
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
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
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
D004983 Ethanolamines AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives. Aminoethanols
D006098 Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS. Granulocyte
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

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