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

      The Journal of Allergy and Clinical Immunology
      Adrenergic beta-Agonists, pharmacology, Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, analysis, chemistry, genetics, physiology, Signal Transduction

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          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.

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