Molecular regulation of the β2-adrenergic receptor by long- and short-acting β-agonists

  • Sheila Collins
  • S. Wang
Conference paper


Prolonged exposure to β-agonists significantly decreases β-adrenergic receptor (βAR)-stimulated adenylyl cyclase activity and receptor number in a variety of tissues or cells, including the airway. This phenomena is referred to a desensitization, and includes both short-term receptor uncoupling from G proteins and longer term receptor down-regulation. Salmeterol, a new β2AR-selective agonist, is widely used as one of the most effective, long-acting bronchodilators for the treatment of nocturnal asthma. Interestingly, it can remain efficacious for as long as 12 hours without promoting functional desensitization. Despite its unique characteristics of resistance to desensitization, the effect of salmeterol on the β2AR-adenylyl cyclase system has not been fully understood. We have previously demonstrated that the β2AR gene can be transcriptionally regulated by its own second messenger, cAMP, through the binding and activation of cAMP response element binding protein (CREB). The present study attempted to explore the molecular regulation of the β2AR by salmeterol in comparison with the shorter-acting βAR-agonist isoproterenol in human bronchial epithelial BEAS2B cells, a cell line which has been widely used as a model for under-standing the regulation of β2AR in the human airway. Our results demonstrates that brief stimulation (10 min) of cells with 10 nM salmeterol produced a modest, but persistant, stimulation of intracellular cAMP levels over several hours. Moreover, during a period of chronic exposure, salmeterol-treated cells do not display the down-regulation of β2AR mRNA levels as observed in isoproterenol-treated cells. Thus, this differential effect on salmeterol on β2AR gene expression may contribute to the ability of this agonist to sustain β2AR-mediated responsiveness, maintaining β2AR number and functional signal transduction. We present a working model to interpret these results.


Adenylyl Cyclase Airway Smooth Muscle cAMP Response Element Binding Adenylyl Cyclase Activity Human Bronchial Epithelial Cell Line 
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Copyright information

© Springer-Verlag/Wien 1998

Authors and Affiliations

  • Sheila Collins
    • 1
  • S. Wang
    • 1
  1. 1.Duke University Medical CenterDurhamUSA

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