Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation.
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.
Johnson
Malcolm
M
GlaxoSmithKline Research and Development, Greenford Road, Middlesex UB6 0HE, United Kingdom. malcolm.w.johnson@gsk.com
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2