Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases.
Journal
Current opinion in pharmacology
ISSN: 1471-4973
Titre abrégé: Curr Opin Pharmacol
Pays: England
ID NLM: 100966133
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
14
02
2020
revised:
17
04
2020
accepted:
22
05
2020
pubmed:
6
7
2020
medline:
10
8
2021
entrez:
5
7
2020
Statut:
ppublish
Résumé
The second messenger molecule 3'5'-cyclic adenosine monophosphate (cAMP) imparts several beneficial effects in lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). While cAMP is bronchodilatory in asthma and COPD, it also displays anti-fibrotic properties that limit fibrosis. Phosphodiesterases (PDEs) metabolize cAMP and thus regulate cAMP signaling. While some existing therapies inhibit PDEs, there are only broad family specific inhibitors. The understanding of cAMP signaling compartments, some centered around lipid rafts/caveolae, has led to interest in defining how specific PDE isoforms maintain these signaling microdomains. The possible altered expression of PDEs, and thus abnormal cAMP signaling, in obstructive lung diseases has been poorly explored. We propose that inhibition of specific PDE isoforms can improve therapy of obstructive lung diseases by amplifying specific cAMP signals in discreet microdomains.
Identifiants
pubmed: 32622335
pii: S1471-4892(20)30021-7
doi: 10.1016/j.coph.2020.05.002
pmc: PMC7529846
mid: NIHMS1600658
pii:
doi:
Substances chimiques
Isoenzymes
0
Phosphodiesterase Inhibitors
0
Cyclic AMP
E0399OZS9N
Phosphoric Diester Hydrolases
EC 3.1.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
34-42Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM107094
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL058506
Pays : United States
Organisme : NHLBI NIH HHS
ID : R29 HL058506
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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