Cyclic nucleotide signalling compartmentation by PDEs in cultured vascular smooth muscle cells.
Animals
Cells, Cultured
Cyclic AMP
/ metabolism
Cyclic GMP
/ metabolism
Male
Myocytes, Smooth Muscle
/ drug effects
Nucleotides, Cyclic
/ metabolism
Phosphodiesterase Inhibitors
/ pharmacology
Phosphoric Diester Hydrolases
/ metabolism
Rats, Wistar
Signal Transduction
/ drug effects
Sildenafil Citrate
/ pharmacology
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
07
09
2017
revised:
04
02
2019
accepted:
10
02
2019
pubmed:
3
3
2019
medline:
1
9
2020
entrez:
3
3
2019
Statut:
ppublish
Résumé
Up-regulation of phosphodiesterases (PDEs) is associated with several vascular diseases, and better understanding of the roles of each PDE isoform in controlling subcellular pools of cyclic nucleotides in vascular cells is needed. We investigated the respective role of PDE1, PDE5, and PDE9 in controlling intracellular cAMP and/or cGMP concentrations ([cAMP] We used selective inhibitors of PDE1 (PF-04471141), PDE5 (sildenafil), and PDE9 (PF-04447943) to measure cAMP- and cGMP-PDE activities with a radioenzymatic assay, in RASMC extracts. Real-time [cAMP] PDE1, PDE5, and PDE9 represented the major cGMP-hydrolyzing activity in RASMCs. Basal PDE1 exerted a functional role in degrading in situ the cGMP produced in response to activation of particulate GC by C-type natriuretic peptide. In high intracellular Ca Our data emphasize the distinct roles of PDE1, PDE5, and PDE9 in local regulation of [cAMP]
Sections du résumé
BACKGROUND AND PURPOSE
Up-regulation of phosphodiesterases (PDEs) is associated with several vascular diseases, and better understanding of the roles of each PDE isoform in controlling subcellular pools of cyclic nucleotides in vascular cells is needed. We investigated the respective role of PDE1, PDE5, and PDE9 in controlling intracellular cAMP and/or cGMP concentrations ([cAMP]
EXPERIMENTAL APPROACH
We used selective inhibitors of PDE1 (PF-04471141), PDE5 (sildenafil), and PDE9 (PF-04447943) to measure cAMP- and cGMP-PDE activities with a radioenzymatic assay, in RASMC extracts. Real-time [cAMP]
KEY RESULTS
PDE1, PDE5, and PDE9 represented the major cGMP-hydrolyzing activity in RASMCs. Basal PDE1 exerted a functional role in degrading in situ the cGMP produced in response to activation of particulate GC by C-type natriuretic peptide. In high intracellular Ca
CONCLUSIONS AND IMPLICATIONS
Our data emphasize the distinct roles of PDE1, PDE5, and PDE9 in local regulation of [cAMP]
Identifiants
pubmed: 30825186
doi: 10.1111/bph.14651
pmc: PMC6514293
doi:
Substances chimiques
Nucleotides, Cyclic
0
Phosphodiesterase Inhibitors
0
Sildenafil Citrate
BW9B0ZE037
Cyclic AMP
E0399OZS9N
Phosphoric Diester Hydrolases
EC 3.1.4.-
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1780-1792Informations de copyright
© 2019 The British Pharmacological Society.
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