Extracellular purines, including ATP and adenosine (ADO), are important neurotransmitter and neuromodulator in the central nervous system (CNS). Purine concentration is controlled by purine release and metabolisms. Astrocytes play important role in purine metabolisms in the CNS. In our previous study, we have shown that fibroblast growth factor 2 (FGF2) upregulates purine metabolic enzymes in rat spinal cord astrocytes. In this study, we investigated the effects of FGF2 on purine metabolisms in rat cortical astrocytes.

Cultured astrocytes from rat cerebral cortex were treated with FGF2. Enzymatic activity for purine metabolism was measured by incubation with extracellular solution containing ATP, AMP or ADO and measurement of those metabolites with HPLC. The expression levels of enzymes were measured by real-time PCR.

In cultured cortical astrocytes, FGF2 increased the mRNA and activity of ecto-5'-nucleotidase (CD73) and adenosine deaminase (ADA), and decreased those of ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2). An FGF receptor inhibitor, SU5402, inhibited the changes in the expression and activity of CD73, ADA and ENTPD2. U0126, a MEK inhibitor, and SP600125, a JNK inhibitor, inhibited the increase of CD73 and ADA, respectively. On the other hand, neither U0126 nor SP600125 inhibited the decrease of ENTPD2.

These results indicate that FGF2 modulates the expression and activity of CD73, ADA and ENTPD2 through FGF receptor. Furthermore, it is suggested that different intracellular signaling pathways are involved in modulation of each purine metabolic enzymes.