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The relationship between oxygen and adenosine in astrocytic cultures
Author(s) -
Kulik Tobias B.,
Aronhime Shimon N.,
Echeverry German,
Beylin Alex,
Winn H. Richard
Publication year - 2010
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21011
Subject(s) - adenosine , biology , extracellular , nucleoside , hypoxia (environmental) , glutamate receptor , catabolism , endocrinology , medicine , cerebral blood flow , oxygen tension , metabolism , oxygen , biochemistry , receptor , chemistry , organic chemistry
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.