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) <or= 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.
Kulik
Tobias B
TB
Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York.
Aronhime
Shimon N
SN
Echeverry
German
G
Beylin
Alex
A
Winn
H Richard
HR
D000227:Adenine Nucleotides / Q000378:metabolism / Q000502:physiology; D000241:Adenosine / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D045604:Extracellular Fluid / Q000378:metabolism; D019271:Hypoxanthine / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology; D007288:Inosine / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats
D000227:Adenine Nucleotides; D019271:Hypoxanthine; D007288:Inosine; D000241:Adenosine; D010100:Oxygen