The second messenger cyclic nucleotides, cyclic AMP and cyclic GMP, mediate relaxation of airways smooth muscle and suppression of multiple inflammatory cell functions. The intracellular concentrations of these cyclic nucleotides are regulated by a superfamily of phosphodiesterase (PDE) enzymes which break down cAMP and cGMP and, thereby, affect airway tone and inflammation. Theophylline and other drugs that act through inhibition of PDE are currently the subject of great research interest, since the uncovering of their anti-inflammatory actions suggests a possible additional mode of action in inflammatory diseases such as asthma. The characterisation of multiple families of PDE isoenzymes with distinct tissue distributions has encouraged hope that selective PDE inhibitors can be developed which act at specific targets without exhibiting the side effects of non-selective inhibitors like theophylline. The combination of bronchodilator and anti-inflammatory properties in a single drug by selective inhibition of specific PDE isoenzymes could produce agents most efficacious in every way for asthma therapy.
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