Comparison of the anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung.
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.
Whelan
C J
CJ
Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd., Ware, Herts.
Johnson
M
M
Vardey
C J
CJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D006098:Granulocytes / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*; D000068299:Salmeterol Xinafoate; D012867:Skin / Q000166:cytology / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D004983:Ethanolamines; D010972:Platelet Activating Factor; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D006632:Histamine; D000420:Albuterol; D000068759:Formoterol Fumarate