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Rat cultured astrocytes release guanine‐based purines in basal conditions and after hypoxia/hypoglycemia
Author(s) -
Ciccarelli Renata,
Di Iorio Patrizia,
Giuliani Patricia,
D'Alimonte Iolanda,
Ballerini Patrizia,
Caciagli Francesco,
Rathbone Michel P.
Publication year - 1999
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/(sici)1098-1136(19990101)25:1<93::aid-glia9>3.0.co;2-n
Subject(s) - biology , hypoglycemia , hypoxia (environmental) , guanine , purine metabolism , basal (medicine) , endocrinology , medicine , neuroscience , biochemistry , enzyme , nucleotide , gene , chemistry , organic chemistry , oxygen , insulin , diabetes mellitus
Abstract Brain ischemia stimulates release from astrocytes of adenine‐based purines, particularly adenosine, which is neuroprotective. Guanosine, which has trophic properties that may aid recovery following neurological damage, is present in high local concentrations for several days after focal cerebral ischemia. We investigated whether guanine‐based purines, like their adenine‐based counterparts, were released from astrocytes and whether their release increased following hypoxia/hypoglycemia. HPLC analysis of culture medium of rat astrocytes showed spontaneous release of endogenous guanine‐based purines at a higher rate than their adenine‐based counterparts. The concentration of guanosine (≈120 nM) and adenosine (≈43 nM) in the culture medium remained constant, whereas concentrations of adenine and guanine nucleotides, particularly GMP, and their metabolites increased with time. Exposure of the cultures to hypoxia/hypoglycemia for 30 min increased the extracellular concentration of adenine‐based purines by 2.5‐fold and of guanine‐based purines by 3.5‐fold. Following hypoxia/hypoglycemia extracellular adenine nucleotide levels increased further. Adenosine concentration increased, but not proportionally to nucleotide levels. Accumulation of adenosine metabolites indicated it was rapidly metabolized. Conversely, the concentrations of extracellular guanine‐based nucleotides remained elevated and the concentration of guanosine continued to increase. These data indicate that astrocytes are a major source of guanine‐based purines, the release of which is markedly increased following hypoxia/hypoglycemia, permitting them to exert neurotrophic effects. GLIA 25:93–98, 1999. © 1999 Wiley‐Liss, Inc.