Phosphodiesterase 4 and tolerance to beta(2)-adrenoceptor agonists in asthma

beta(2)-Adrenoceptor agonists provide a mainstay in the treatment of asthma worldwide. However, despite their ability to provide symptomatic relief, chronic or repeated exposure to beta(2)-adrenoceptor agonists does not resolve asthmatic inflammation, because of the rapid development of tolerance by pro-inflammatory and immune cells of the lung. The prevailing belief is that tolerance to the so-called non-bronchodilator actions of beta(2)-adrenoceptor agonists is largely attributable to direct receptor desensitization mediated by G protein receptor-coupled kinases and/or cAMP-dependent protein kinase, Here, Mark Giembycz suggests another, largely ignored, explanation for beta(2)-adrenoceptor desensitization that is based on the accelerated degradation of cAMP by phosphodiesterase.