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], reached 10(-7) M to 10(-6) M with a pO(2) of 30-10 mmHg, 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. (C) 2010 Wiley-Liss, Inc.