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Trends Pharmacol Sci. 1994 Oct;15(10):370-4.

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

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Department of Inflammation and Respiratory Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.


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.

[Indexed for MEDLINE]

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