Adenosine protects cultured retinal neurons against NMDA-induced cell death through A1 receptors

PURPOSE: To determine whether adenosine can protect cultured retinal neurons, consisting mainly of amacrine cells, from N-methyl-D-aspartate (NMDA)-induced neurotoxicity, and to determine whether agonists and antagonists of adenosine receptors also have a protective effect. METHODS: Cultured retinal neurons obtained from fetal Wistar rats (gestational age 18-19 days) were maintained for 10-11 days. Neurons were exposed to NMDA (1.0 mM) for 10 min with or without adenosine or to NMDA with adenosine receptor agonists or antagonists. Neuronal death was assessed by the trypan-blue exclusion method 24 hr after the exposure. RESULTS: Adenosine at doses of 0.01 microM and higher significantly protected (p < 0.05, Dunnett) primary cultured fetal rat retinal neurons from apoptotic and/or necrotic death induced by NMDA (1.0 mM). The protective effect of adenosine (10 microM) against NMDA-induced neuronal death was lost by simultaneous exposure to selective A1 receptor antagonist but not to A2a receptor antagonist. Selective A1 receptor agonists had similar effects as adenosine, but A2a receptor agonists and 8-Br-cyclic AMP had no effect on cell viability. CONCLUSIONS: Adenosine can protect cultured retinal neurons against NMDA-induced cell death via the A1 receptor.