Notes On Cyclic Enzymes And Its Effect On The Regulation Of Airway Smooth Muscle

1785 Words Sep 15th, 2014 8 Pages
Cyclic adenosine 3’,5’-monophosphate (cAMP) plays an important role in the activation and recruitment of inflammatory cells into airways and in the regulation of airway smooth muscle (ASM) tone [1]. Elevation of cAMP levels leads to ASM relaxation and bronchodilation; it also inhibits a number of immune and inflammatory responses, including T-cell activation and proliferation, tumour necrosis factor (TNF)-α production in monocytes and macrophages, superoxide anion production in eosinophils, and eosinophil chemotaxis by inflammatory mediators [2]. The amount of cAMP can increase within cells by inhibiting several cyclic nucleotide phosphodiesterases (PDE) [1].
PDE4 is the predominant PDE expressed in neutrophils, T cells and macrophages and therefore its inhibition may also have inhibitory effects upon both inflammatory and immune cells [1].
Chronic inflammation plays a central role in chronic obstructive pulmonary disease (COPD), and is characterized by an increase in neutrophils, macrophages and CD8+ T lymphocytes in small and large airways as well as in lung parenchyma and pulmonary vasculature [2]. Therefore, it is not surprising that over the past two decades or so, many researchers are interested in the cAMP-specific PDE4 family because they considered it a potential intracellular target that could be exploited to therapeutic advantage for COPD and a multitude of diseases associated COPD [4].
Many PDE4 inhibitors were tested in recent years, and numerous studies with…

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