| Phosphodiesterases terminate the cAMP signal
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Phosphodiesterases (PDEs) terminate the cAMP signal by converting cAMP to its 5'AMP metabolite (see Fig. 38.4); thus they have the potential to play key roles in the regulation of various physiologic responses in many different cells and tissues. Indeed, they have been postulated to regulate platelet activation, vascular relaxation, cardiac muscle contraction, and inflammation, making them attractive targets for the development of selective inhibitors as potential therapeutic agents. For example, one group of compounds, the methylxanthines - which include theophylline and isobutylmethylxanthine - have been used as bronchodilators in the treatment of asthma, and are also able to exert positive inotropic responses in the heart. Moreover, drugs selective for the PDE3 class of enzymes - such as milrinone - are cardiotonic and increase the force of contraction of the heart, presumably by increasing the concentrations of cAMP and stimulating PKA, leading to phosphorylation of cardiac calcium channels and a subsequent increase in intracellular calcium concentration.
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