1. Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?
- Author
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Theron AJ, Steel HC, Tintinger GR, Feldman C, and Anderson R
- Subjects
- Animals, Gene Expression Regulation drug effects, Humans, Inflammation genetics, Inflammation immunology, Inflammation metabolism, Inflammation Mediators metabolism, Receptors, Adrenergic, beta-2 metabolism, Signal Transduction drug effects, Treatment Outcome, Adrenergic beta-2 Receptor Agonists therapeutic use, Anti-Inflammatory Agents therapeutic use, Inflammation drug therapy, Receptors, Adrenergic, beta-2 drug effects
- Abstract
Beta2-adrenoreceptor agonists (β2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled β2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of β2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of β2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of β2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3',5'-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells.
- Published
- 2013
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