| Abstract: | Brain tissue oxygenation affects cerebral function and blood flow (CBF). Adenosine (Ado), a purine nucleoside, moderates neuronal activity, and arterial diameter. The cellular source of Ado in brain remains elusive; however, astrocytes are a logical site of production. Using astrocytic cultures, we tested the hypothesis that astrocytic derived Ado reflects cerebral oxygenation. We found that during alterations in pO2, extracellular levels of Ado [Ado]e changed rapidly. Graded reductions of oxygen tension revealed that[Ado]e reached 10−7 M to 10−6 M with a pO2 of 30–10mmHg, comparable with [Ado]e and oxygen levels found in brain tissue during normoxemia. Higher O2 levels were associated with a depression of [Ado]e. Under conditions of low pO2 (pO2 ≤ 3 mmHg), inhibition of extracellular catabolism of adenosine monophosphate (AMP) prevented an increase of [Ado]e and resulted in a rise in [AMP]e. The rise in [AMP]e preceded the increase in [Ado]e. In the presence of nucleoside transporter inhibitors, accumulation of [Ado]e persisted. On the basis of our studies in culture we conclude that astrocytes are a significant source of Ado and that during hypoxia, the changes in [Ado]e are in a range to affect both neuronal activity as well as CBF. © 2010 Wiley‐Liss, Inc. |
