Adenosine A2a receptor induces GDNF expression by the Stat3 signal in vitro.

Adenosine A2a receptor (A2aR) is believed to play a role in a number of physiological responses and pathological conditions. Our group has shown previously that A2aR-activated astrocytes occurred following oxygen-glucose deprivation. However, the relationship between A2aR and neurotrophins is poorly understood. Here, we investigate the effect of A2aR on glial cell line-derived neurotrophic factor (GDNF) expression in rat brain astrocyte-2 (RBA-2) cells by quantitative PCR and western blot. We established a stable A2aR-overexpressing cell line and found that A2aR induced GDNF expression both at mRNA and protein levels. A2aR-selective antagonist Sch58261 decreased GDNF expression in a dose-dependent manner with increased activation of Stat3. The Stat3 inhibitor reversed the effect of Sch58261 on GDNF expression. Therefore, these data indicate that A2aR induces GDNF expression by the Stat3 pathway, which provides a new insight into the function of A2aR in cerebral ischemia and neuroprotection.