PHOSPHODIESTERASE-4 AND TOLERANCE TO BETA(2)-ADRENOCEPTOR AGONISTS INASTHMA

beta(2)-Adrenoceptor agonists provide a mainstay in the treatment of a sthma 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 develop ment of tolerance by pro-inflammatory and immune cells of the lung. Th e prevailing belief is that tolerance to the so-called non-bronchodila tor actions of beta(2)-adrenoceptor agonists is largely attributable t o direct receptor desensitization mediated by G protein receptor-coupl ed kinases and/or cAMP-dependent protein kinase, Here, Mark Giembycz s uggests another, largely ignored, explanation for beta(2)-adrenoceptor desensitization that is based on the accelerated degradation of cAMP by phosphodiesterase.