Endogenous cyclic AMP-adenosine pathway regulates cardiac fibroblast growth

Our previous studies show that cardiac fibroblasts express the extracellular "cAMP-adenosine pathway," that is, the generation of adenosine from extracelluar cAMP. The goal of this study was to assess whether activation of the cAMP-adenosine pathway by stimulation of endogenous cAMP synthe...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2001-04, Vol.37 (4), p.1095-1100
Main Authors: DUBEY, Raghvendra K, GILLESPIE, Delbert G, ZAICHUAN MI, JACKSON, Edwin K
Format: Article
Language:English
Subjects:
Adenosine - metabolism
Adenosine Deaminase Inhibitors
Adenosine Kinase - antagonists & inhibitors
Adenylyl Cyclase Inhibitors
Adrenergic alpha-Agonists - pharmacology
Adrenergic beta-Agonists - pharmacology
Analysis of Variance
Animals
Biological and medical sciences
Cell Division - drug effects
Colforsin - pharmacology
Cyclic AMP - metabolism
DNA - biosynthesis
Fibroblasts - physiology
Fundamental and applied biological sciences. Psychology
Heart
Isoproterenol - pharmacology
Male
Myocardium - cytology
Myocardium - metabolism
Norepinephrine - pharmacology
Protein Biosynthesis
Purinergic P1 Receptor Antagonists
Rats
Rats, Sprague-Dawley
Vertebrates: cardiovascular system
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Summary:Our previous studies show that cardiac fibroblasts express the extracellular "cAMP-adenosine pathway," that is, the generation of adenosine from extracelluar cAMP. The goal of this study was to assess whether activation of the cAMP-adenosine pathway by stimulation of endogenous cAMP synthesis regulates cardiac fibroblast growth. Cardiac fibroblasts in 3D cultures were used as the model system. Treatment of cardiac fibroblasts with forskolin, isoproterenol, or norepinephrine increased cAMP production and extracellular levels of adenosine, and these effects were prevented by inhibition of adenylyl cyclase (2',5'-dideoxyadenosine). Treatment with forskolin, isoproterenol, or norepinephrine for 24 hours inhibited DNA synthesis ((3)H-thymidine incorporation), and this effect was enhanced by combined inhibition of adenosine deaminase (erythro-9-[2-hydroxy-3-nonyl] adenine) plus adenosine kinase (iodotubercidin). Inhibition of adenylyl cyclase or adenosine receptors (1,3-dipropyl-8-p-sulfophenylxanthine or KF17837) prevented the effects of forskolin, isoproterenol, and norepinephrine on DNA synthesis. Forskolin also inhibited protein synthesis ((3)H-leucine incorporation) and cell proliferation, and these effects were blocked by adenosine receptor antagonism. Treatment of cardiac fibroblasts with norepinephrine for >48 hours but not
ISSN:0194-911X
1524-4563
DOI:10.1161/01.hyp.37.4.1095