title: beta-Adrenoceptor inverse agonists in asthma.
abstract: Beta(2)-adrenoceptor (beta(2)-AR) agonists are very effective bronchodilators and play a major role in every stage of asthma management. However, their chronic, regular use is associated with detrimental effects including an increase in asthma-related deaths. Conversely, recent data suggest that certain beta-blockers, specifically beta-adrenoceptor (beta-AR) inverse agonists, may be useful in the chronic treatment of asthma. Here we review the data for this observation and the signaling pathways that may be involved. The data suggest that beta(2)-AR signaling is required to produce maximal airway inflammation and hyperresponsiveness, and the signaling pathway responsible for these effects is likely the non-canonical beta-arrestin-2 pathway. Therefore, beta-AR inverse agonists may produce their beneficial chronic effects by inhibiting constitutive or ligand-induced activation of this pathway. Both lung parenchymal and hematopoietic cells appear to be involved in mediating the beneficial effects of beta-AR inverse agonists.
authors.affiliation: Department of Pulmonary Medicine, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Burton F
authors.initials: BF
authors.lastname: Dickey
authors.forename: Julia K L
authors.initials: JK
authors.lastname: Walker
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bond
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D054314:Drug Inverse Agonism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents
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