Phosphodiesterases as therapeutic targets for respiratory diseases

Haoxiao Zuo; Isabella Cattani-Cavalieri; Nshunge Musheshe; Viacheslav O Nikolaev; Martina Schmidt

doi:10.1016/j.pharmthera.2019.02.002

Phosphodiesterases as therapeutic targets for respiratory diseases

Pharmacol Ther. 2019 May:197:225-242. doi: 10.1016/j.pharmthera.2019.02.002. Epub 2019 Feb 10.

Authors

Haoxiao Zuo¹, Isabella Cattani-Cavalieri², Nshunge Musheshe³, Viacheslav O Nikolaev⁴, Martina Schmidt⁵

Affiliations

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.

PMID: 30759374
DOI: 10.1016/j.pharmthera.2019.02.002

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.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Animals
Humans
Lung Diseases / drug therapy*
Lung Diseases / enzymology
Phosphodiesterase Inhibitors / therapeutic use*
Phosphoric Diester Hydrolases / metabolism*

Substances

Phosphodiesterase Inhibitors
Phosphoric Diester Hydrolases