Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides and purines in rat striatum during transient ischemia.
Extracellular (EC) adenosine, hypoxanthine, xanthine, and inosine concentrations were monitored in vivo in the striatum during steady state, 15 min of complete brain ischemia, and 4 h of reflow and compared with purine and nucleotide levels in the tissue. Ischemia was induced by three-vessel occlusion combined with hypotension (50 mm Hg) in male Sprague-Dawley rats. EC purines were sampled by microdialysis, and tissue adenine nucleotides and purine catabolites were extracted from the in situ frozen brain at the end of the experiment. ATP, ADP, and AMP were analyzed with enzymatic fluorometric techniques, and adenosine, hypoxanthine, xanthine, and inosine with a modified HPLC system. Ischemia depleted tissue ATP, whereas AMP, adenosine, hypoxanthine, and inosine accumulated. In parallel, adenosine, hypoxanthine, and inosine levels increased in the EC compartment. Adenosine reached an EC concentration of 40 microM after 15 min of ischemia. Levels of tissue nucleotides and purines normalized on reflow. However, xanthine levels increased transiently (sevenfold). In the EC compartment, adenosine, inosine, and hypoxanthine contents normalized slowly on reflow, whereas the xanthine content increased. The high EC levels of adenosine during ischemia may turn off spontaneous neuronal firing, counteract excitotoxicity, and inhibit ischemic calcium uptake, thereby exerting neuroprotective effects.
D000241:Adenosine / Q000032:analysis*; D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry; D005110:Extracellular Space / Q000032:analysis*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000032:analysis*; D007288:Inosine / Q000032:analysis*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009711:Nucleotides / Q000032:analysis*; D011687:Purines / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D019820:Xanthine; D014970:Xanthines / Q000032:analysis*
D007042:Hypoxanthines; D009711:Nucleotides; D011687:Purines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D000249:Adenosine Monophosphate; D007288:Inosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine