Cyclic AMP and the Control of Airways Smooth Muscle Tone

As little as a decade ago, most information concerning the role of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) as a second messenger mediating bronchorelaxation was inferred from studies on vascular smooth muscle. Much has changed since that time. Airways smooth muscle itself has become the target of considerable scientific investigation focused on the molecular mechanisms responsible for the relaxant activity of β-adrenoceptor agonists and other agents that activate adenylyl cyclase. In many ways the information gained from thes studies reinforces the traditional concept that the action of β-adrenoceptor agonists on airways smooth muscle is mediated by a cyclic AMP-regulated protein phosphorylation cascade system, with cyclic AMP-dependent protein kinase (protein kinase A) serving as the intra- cellular target enzyme for cyclic AMP. Recently, however, data have emerged that suggest an alternative mechanism by which cyclic AMP can relax airways smooth muscle. Still other data have prompted th near-heretical proposal that bronchorelaxation in response to β-adrenoceptor agonists is mediated, at least in part, by a cyclic AMP-independent mechanism.

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  1. Department of Inflammation and Respiratory Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA Theodore J. Torphy
  2. Division of Therapeutics, University Hospital, Queen’s Medical Centre, Nottingham, UK Ian P. Hall
  1. Theodore J. Torphy
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  1. Department Head Discovery Biology, Rhône-Poulenc Rorer Ltd, Dagenham Research Centre, RM10 7XS, Dagenham, Essex, England David Raeburn
  2. Department of Thoracic Medicine, Royal Brompton National Heart and Lung Institute, Dovehouse Street, SW3 6LY, London, England Mark A. Giembycz ( Lecturer ) ( Lecturer )

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Torphy, T.J., Hall, I.P. (1994). Cyclic AMP and the Control of Airways Smooth Muscle Tone. In: Raeburn, D., Giembycz, M.A. (eds) Airways Smooth Muscle: Biochemical Control of Contraction and Relaxation. Respiratory Pharmacology and Pharmacotherapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7681-0_10

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