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J Allergy Clin Immunol. 2006 Jan;117(1):18-24; quiz 25.

Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation.

Author information

1
GlaxoSmithKline Research and Development, Greenford Road, Middlesex UB6 0HE, United Kingdom. malcolm.w.johnson@gsk.com

Abstract

The human beta(2)-adrenoceptor is a member of the 7-transmembrane family of receptors, encoded by a gene on chromosome 5, and widely distributed in the respiratory tract. Intracellular signaling after beta(2)-adrenoceptor activation is largely affected through cyclic adenosine monophosphate and protein kinase A. Differences in the mechanism of interaction of short- and long-acting beta(2)-agonists and the beta(2)-receptor are reflected in the kinetics of airway smooth muscle relaxation and the onset and duration of bronchodilation in asthmatic patients. beta-Adrenoceptor desensitization associated with prolonged beta(2)-agonist activation differs depending on the cell type and is reflected in different profiles of clinical tolerance to chronic beta(2)-agonist therapy. A number of genetic polymorphisms of the beta(2)-receptor have been described that appear to alter the behavior of the receptor, including the response to beta(2)-agonists. The synergy between the beta(2)-receptor and the glucocorticoid receptor functions has implications for the combined use of beta(2)-agonists and corticosteroids in the treatment of respiratory disease.

PMID:
16387578
DOI:
10.1016/j.jaci.2005.11.012
[Indexed for MEDLINE]

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