Beta-adrenoceptors, cAMP and airway smooth muscle relaxation: challenges to the dogma

Trends Pharmacol Sci. 1994 Oct;15(10):370-4. doi: 10.1016/0165-6147(94)90157-0.


beta-Adrenoceptor agonists are assumed to induce airway smooth muscle relaxation through the cAMP-protein kinase A (PKA) phosphorylation cascade system. This traditional second messenger paradigm of beta-adrenoceptor agonist action is deeply engrained, but in this article Theodore Torphy reviews recent observations that force a re-examination of the dogma. For example, cAMP can activate protein kinase G as well as PKA, and this unanticipated dual action may contribute to the relaxant activity of cAMP. Other studies suggest that beta-adrenoceptor agonists can induce relaxation by a cAMP-independent mechanism involving a direct coupling of the beta-adrenoceptor to Ca(2+)-dependent K+ channels. Consequently, it is possible that multiple cAMP-dependent pathways act in concert with cAMP-independent pathways to mediate bronchodilation in response to beta-adrenoceptor agonists.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Humans
  • Muscle Relaxation
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Second Messenger Systems


  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases