β2-Adrenoceptor Function in Asthma.
journal contributionposted on 2017-11-01, 10:32 authored by Yassine Amrani, Peter Bradding
β2-adrenoceptor agonists, often used in combination with corticosteroids, have been extensively used for the treatment of asthma. However, concerns have been raised regarding their adverse effects and safety including poor asthma control, life-threatening exacerbations, exacerbations that often require hospitalization, and asthma-related deaths. The question as to whether these adverse effects relate to the loss of their bronchoprotective action remains an interesting possibility. In the chapter, we will review the experimental evidence that describes the different potential factors and associated mechanisms that can blunt the therapeutic action of β2-adrenoceptor agonists in asthma. We show here evidence that various key inflammatory cytokines, growth factors, some respiratory viruses, certain allergens, unknown factors present in serum from atopic asthmatics have the capacity to impair β2-adrenoceptor function in airway smooth muscle, the main target of these drugs. More importantly, we present our latest research describing the role played by mast cells in impairing β2-adrenoceptor function. Although no definitive conclusion could be made regarding the implication of one single mechanism, receptor uncoupling, or receptor desensitization due to phosphorylation represents the main inhibitory pathways associated with a loss of β2-adrenoceptor function in airway smooth muscle. Targeting the pathways leading to β2-adrenoceptor dysfunction will likely provide novel therapies to improve the efficacy of β2-agonists in asthma.
The research was supported by the NIHR Leicester Biomedical Research Centre
CitationAdvances in Immunology, 2017, 136, pp. 1-28
Author affiliation/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation
- AM (Accepted Manuscript)