doi: 10.1161/01.RES.0000174112.36064.77
© 2005 American Heart Association, Inc.
Editorials |
Control of Adenosine Transport by Hypoxia
From Experimental Pediatric Cardiology, Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich at the TU Munich, Germany.
Correspondence to Dr Agnes Görlach, Experimental Pediatric Cardiology, Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich at the TU Munich, Lazarettstr. 36, 80636 Munich, Germany. E-mailgoerlach@dhm.mhn.de
See related article, pages 16–24
Key Words: hypoxia • adenosine • equilibrative nucleoside transporter • nitric oxide • endothelial cells
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The extracellular accumulation of the nucleoside adenosine is one of the first steps in a protective auto/paracrine signaling cascade aimed at limiting cellular damage in response to adverse conditions including hypoxia or ischemia.1 This adenosine acts as a signal molecule that is able to mediate numerous physiological and metabolic effects that could be beneficial to hypoxic cells including vasodilation, stimulation of glycogen breakdown to provide glucose for ATP production via anaerobic glycolysis and reduction of neuronal excitability as well as neurotransmitter release to reduce neuronal energy requirements.2
These intracellular effects of adenosine are mediated by 4 subtypes of G-protein–coupled adenosine receptors (AR) (A1, A2A, A2B, and A3) which differ in their expression profiles in defined cell types, the type of G-proteins to which they are coupled and their sensitivity to control by receptor phosphorylation.3 Endothelial cells predominantly express the A2A and A2BAR subtypes. The expression of both subtypes is regulated by hypoxia, such that low pO2 induces A2BAR expression, which promotes the expression of angiogenic factors and reduction of A2AAR expression.4 The expression of the AR is further stimulated by increased extracellular adenosine during hypoxia.3 Adenosine released from the endothelium during systemic hypoxia acts back on AR on the endothelium to increase the synthesis of nitric oxide (NO) which then causes vasodilatation.5 Therefore, the regulation of extracellular adenosine levels is critical for the interaction of adenosine with its receptors and subsequent responses that modify cell function in response to hypoxia.
Adenosine can be
Related Article:
Circ. Res. 2005 97: 16-24.
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