Effects of adenosine deaminase inhibition on active uptake and metabolism of adenosine in astrocytes in primary cultures.
The use of a relatively specific adenosine deaminase inhibitor, 2'-deoxycoformycin (1.0 microM), has revealed an active transport of adenosine into astrocytes in primary cultures. The abolishment of part of the metabolic degradation and of a concentration gradient, which may favour influx, did not lead to a decreased total uptake. The concentration of labelled, i.e. exchangeable adenosine rose to become several fold higher than in the medium. Thus, as previously shown in neurons, the uptake of adenosine into astrocytes occurs by an active and concentrative process. As a result of the increase in the adenosine concentration when the inhibitor was present, evidence for an increased phosphorylation to the nucleotides (i.e. ATP, ADP, AMP) was obtained. This is in contrast to previous findings in neurons where the incorporation of labelled adenosine into these compounds was decreased in the presence of 2'-deoxycoformycin. This difference may suggest that the salvage pathway from inosine to adenine nucleotides is crucial for nucleotide synthesis in neurons, but not in astrocytes.
Matz
H
H
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
Hertz
L
L
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D009700:Nucleoside Deaminases / Q000378:metabolism*; D015649:Pentostatin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine