The relationship between oxygen and adenosine in astrocytic cultures

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 pO 2 , 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 pO 2 of 30–10mmHg, comparable with [Ado] e and oxygen levels found in brain tissue during normoxemia. Higher O 2 levels were associated with a depression of [Ado] e . Under conditions of low pO 2 (pO 2 ≤ 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.