Stimulus- and cell-type-specific release of purines in cultured rat forebrain astrocytes and neurons.
Adenosine is formed during conditions that deplete ATP, such as ischemia. Adenosine deaminase converts adenosine into inosine, and both adenosine and inosine can be beneficial for postischemic recovery. This study investigated adenosine and inosine release from astrocytes and neurons during chemical hypoxia or oxygen-glucose deprivation. In both cell types, 2-deoxyglucose was the most effective stimulus for depleting cellular ATP and for evoking inosine release; in contrast, oxygen-glucose deprivation evoked the greatest adenosine release. alpha,beta-Methylene ADP, an inhibitor of ecto-5'nucleotidase, significantly reduced adenosine release from astrocytes but not neurons. Dipyridamole, an inhibitor of equilibrative nucleoside transporters, inhibited both adenosine and inosine release from neurons. Erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase, reduced neuronal inosine release evoked by oxygen-glucose deprivation but not by 2-deoxyglucose treatment. These data indicate that (1). astrocytes release adenine nucleotides that are hydrolyzed extracellularly to adenosine, whereas neurons release adenosine per se, (2). inosine is formed intracellularly and released via nucleoside transporters, and (3). inosine is formed by an adenosine deaminase-dependent pathway during oxygen-glucose deprivation but not during 2-deoxyglucose treatment. In summary, the metabolic pathways for adenosine formation and release were cell-type dependent whereas the pathways for inosine formation were stimulus dependent.
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada. parkins@ms.umanitoba.ca
Fiona E
FE
Parkinson
Wei
W
Xiong
D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000096:biosynthesis / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D019807:Iodoacetic Acid / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology*; D011687:Purines / Q000378:metabolism*; D051381:Rats; D013268:Stimulation, Chemical
D009840:Oligomycins; D011687:Purines; D007288:Inosine; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005947:Glucose; D000225:Adenine; D000241:Adenosine; D019807:Iodoacetic Acid