ADENOSINE AS AN ENDOGENOUS MEDIATOR OF HYPOXIA FOR INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR MESSENGER-RNA IN U-937 CELLS

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)theophyline, a non-selective adenosine receptor antagonist and DMPX. These results suggest that the hypoxic induction of VEGF mRNA is mediated by adenosine via At-receptor in U-937 cells. (C) 1994 Academic Press, Inc.