Inosine Mediates the Protective Effect of Adenosine in Rat Astrocyte Cultures Subjected to Combined Glucose‐Oxygen Deprivation

: Preliminary evidence suggests adenosine, a neuromodulator, has neuroprotective properties during cerebral ischemia. It is unclear, however, if adenosine has glioprotective effects. We studied the effect of adenosine on cellular injury in astroglial cultures subjected to combined glucose‐oxygen deprivation. Adenosine (100–1,000 µM) dramatically reduced astroglial injury, whereas the adenosine agonists 2‐chloroadenosine (10 nM–100 µM), N6‐cyclopentyladenosine (1 nM–10 µM), 5′‐N‐ethylcarboxamidoadenosine (10 nM–100 µM), and N6‐2‐(4‐aminophenyl)ethyladenosine (10 nM–100 µM) had no effect. Furthermore, the adenosine antagonists 8‐cyclopentyl‐1,3‐dipropylxanthine (1 nM–1 µM), xanthine amine congener (10 nM–10 µM), and 8‐(p‐sulfophenyl)‐theophylline (10–300 µM) failed to reverse the protective effect of 200 µM adenosine. Next, adenosine degradation products were studied. Inosine proved to be glioprotective at concentrations nearly identical to those of adenosine, but hypoxanthine and ribose had no effect. The protective effect of 200 µM inosine was not reversed by 8‐(p‐sulfophenyl)theophylline (10–300 µM). Adenosine deaminase (1 unit/ml) had no effect on protection produced by adenosine, whereas erythro‐9‐(2‐hydroxy‐3‐nonyl)adenine hydrochloride (10 µM) reversed the protective effect of adenosine. Dipyridamole (4 µM) inhibited the protective effect of both adenosine and inosine. We conclude that adenosine dramatically decreases astroglial injury during combined glucose‐oxygen deprivation and that this protective effect appears to be mediated by inosine.