BETA-ADRENOCEPTORS, CAMP AND AIRWAY SMOOTH-MUSCLE RELAXATION - CHALLENGES TO THE DOGMA

beta-Adrenoceptor agonists are assumed to induce airway smooth muscle relaxation through the cAMP-protein kinase A (PKA) phosphorylation cas cade system. This traditional second messenger paradigm of beta-adreno ceptor agonist action is deeply engrained, but in this article Theodor e Torphy reviews recent observations that force a re-examination of th e dogma. For example, cAMP can activate protein kinase G as well as PK A, and this unanticipated dual action may contribute to the relaxant a ctivity of cAMP. Other studies suggest that beta-adrenoceptor agonists can induce relaxation by a cAMP-independent mechanism involving a dir ect coupling of the beta-adrenoceptor to Ca2+-dependent K+ channels. C onsequently, it is possible that multiple cAMP-dependent pathways act in concert with cAMP-independent pathways to mediate bronchodilation i n response to beta-adrenoceptor agonists.