Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2a: Role in modulating secretion
Date
2011
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Article
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Abstract
Catecholamine (CAT) release from chromaffin tissue plays an essential role in the fetus which develops in a low O2 environment (hypoxia). To address molecular mechanisms regulating CAT secretion in low O2, we exposed a fetal chromaffin-derived cell line (MAH cells) to chronic hypoxia (CHox; 2% O2, 24 h) and assessed gene expression using microarrays, quantitative RT-PCR, and western blot. CHox caused a dramatic 12 upregulation of adenosine A2a receptor (A2aR) mRNA, an effect critically dependent upon hypoxia-inducible factor (HIF)-2a which bound the promoter of the A2aR gene. In amperometric studies, acute hypoxia and high K+ (30 mM) evoked quantal CAT secretion that was enhanced after CHox, and further potentiated during simultaneous A2aR activation by adenosine. A2aR activation also enhanced stimulus-induced rise in intracellular Ca2+ in control, but not HIF-2a-deficient, MAH cells. Thus, A2aR, adenosine, and HIF-2a are key contributors to the potentiation of CAT secretion in developing chromaffin cells during chronic hypoxia.
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Citation
Biochemical and Biophysical Research Communications, 2011, 412: 466–472
Keywords
Hypoxia, HIF-2a, Chromaffin-derived MAH cells, Catecholamines, Adenosine, Amperometry, Intracellular Ca2+