The long‐acting β‐adrenoceptor agonist, indacaterol, inhibits IgE‐dependent responses of human lung mast cells

• Published in: British journal of pharmacology 2009-09, Vol.158 (1), p.267-276
• Main Authors: Scola, Anne‐Marie, Loxham, Matthew, Charlton, Steven J, Peachell, Peter T
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; asthma; Biological and medical sciences; bronchodilators; Chronic obstructive pulmonary disease, asthma; Dose-Response Relationship, Drug; histamine; Histamine Release - drug effects; Histamine Release - physiology; Humans; Immunoglobulin E - metabolism; Immunoglobulin E - physiology; Indans - pharmacology; Lung - cytology; Lung - drug effects; Lung - physiology; Mast Cells - drug effects; Mast Cells - physiology; Medical sciences; Pharmacology. Drug treatments; Pneumology; Quinolones - pharmacology; Research Papers; Time Factors; β2‐adrenoceptors
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2009.00178.x

Background and purpose:  The long‐acting β2‐adrenoceptor agonist, indacaterol, has been developed as a bronchodilator for the therapeutic management of respiratory diseases. The aim of the present study was to determine whether indacaterol has any anti‐inflammatory activity. To this end, the effects of indacaterol on human lung mast cell responses were investigated. Experimental approach:  The effects of indacaterol, and the alternative long‐acting β‐agonists formoterol and salmeterol, were investigated on the IgE‐dependent release and generation of histamine, cysteinyl‐leukotrienes and prostaglandin D2 from human lung mast cells. Moreover, the extent to which long‐term (24–72 h) incubation of mast cells with long‐acting β‐agonists impaired the subsequent ability of β‐agonists to inhibit mast cell responses was assessed. Key results:  Indacaterol was as potent and as efficacious as the full agonist, isoprenaline (EC50, ∼4 nmol·L−1), at inhibiting the IgE‐dependent release of histamine from mast cells. Formoterol was a full agonist whereas salmeterol was a partial agonist as inhibitors of histamine release. All three long‐acting β‐agonists were effective inhibitors of the IgE‐dependent generation of cysteinyl‐leukotrienes and prostaglandin D2. Long‐term incubation of mast cells with long‐acting β‐agonists led to a reduction in the subsequent ability of β‐agonists to stabilize mast cell responses. This tendency to induce functional desensitization was least evident for indacaterol. Conclusions and implications:  Indacaterol is an effective inhibitor of the release of mediators from human lung mast cells. This suggests that, as well as bronchodilation, mast cell stabilization may constitute an additional therapeutic benefit of indacaterol.