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Pharmacol Ther. 2019 Feb 10. pii: S0163-7258(19)30015-4. doi: 10.1016/j.pharmthera.2019.02.002. [Epub ahead of print]

Phosphodiesterases as therapeutic targets for respiratory diseases.

Author information

1
Department of Molecular Pharmacology, University of Groningen, the Netherlands; Institute of Experimental Cardiovascular Research, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany. Electronic address: h.zuo@rug.nl.
2
Department of Molecular Pharmacology, University of Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
3
Department of Molecular Pharmacology, University of Groningen, the Netherlands.
4
Institute of Experimental Cardiovascular Research, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany; German Center for Cardiovascular Research (DZHK), 20246 Hamburg, Germany.
5
Department of Molecular Pharmacology, University of Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract

Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, affect millions of people all over the world. Cyclic adenosine monophosphate (cAMP) which is one of the most important second messengers, plays a vital role in relaxing airway smooth muscles and suppressing inflammation. Given its vast role in regulating intracellular responses, cAMP provides an attractive pharmaceutical target in the treatment of chronic respiratory diseases. Phosphodiesterases (PDEs) are enzymes that hydrolyze cyclic nucleotides and help control cyclic nucleotide signals in a compartmentalized manner. Currently, the selective PDE4 inhibitor, roflumilast, is used as an add-on treatment for patients with severe COPD associated with bronchitis and a history of frequent exacerbations. In addition, other novel PDE inhibitors are in different phases of clinical trials. The current review provides an overview of the regulation of various PDEs and the potential application of selective PDE inhibitors in the treatment of COPD and asthma. The possibility to combine various PDE inhibitors as a way to increase their therapeutic effectiveness is also emphasized.

KEYWORDS:

COPD; asthma; cAMP; cGMP; phosphodiesterases

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