Abstract
Adenosine induced by hypoxia exerts various effects via different types of receptors. Recently, hypoxia was shown to be a strong inducer of vascular endothelial growth factor, a secreted endothelial cell specific mitogen. In this report, we studied on effects of adenosine on inducibility of VEGF and possible mediation of hypoxia for its induction in U-937 cells. Hypoxia induced expression of VEGF mRNA with an early peak at 1 hour. 5'-N-ethylcarboxamidoadenosine, an adenosine analog, strongly induced VEGF mRNA, which was inhibited by 3,7-dimethyl-1-propargylxanthine (DMPX), an A2-antagonist. The hypoxic induction was inhibited by adenosine deaminase, 7-(beta-hydroxyethyl)theophylline, a non-selective adenosine receptor antagonist and DMPX. These results suggest that the hypoxic induction of VEGF mRNA is mediated by adenosine via A2-receptor in U-937 cells.
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / pharmacology
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Adenosine / physiology*
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Adenosine Deaminase / pharmacology
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Adenosine-5'-(N-ethylcarboxamide)
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Base Sequence
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Blotting, Northern
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Bucladesine / pharmacology
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Cell Hypoxia
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Cell Line
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Cloning, Molecular
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DNA Primers
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Endothelial Growth Factors / biosynthesis*
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Gene Expression* / drug effects
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Humans
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Lymphokines / biosynthesis*
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Molecular Sequence Data
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Polymerase Chain Reaction / methods
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Purinergic P1 Receptor Antagonists
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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Theobromine / analogs & derivatives
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Theobromine / pharmacology
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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DNA Primers
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Endothelial Growth Factors
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Lymphokines
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Purinergic P1 Receptor Antagonists
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Adenosine-5'-(N-ethylcarboxamide)
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3,7-dimethyl-1-propargylxanthine
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Bucladesine
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Adenosine Deaminase
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Adenosine
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Theobromine