Adenosine triphosphate (ATP) and adenosine are neurotransmitters and neuromodulators in the central nervous system. Astrocytes regulate extracellular concentration of purines via ATP release and its metabolisms via ecto-enzymes. The expression and activity of purine metabolic enzymes in astrocytes are increased under pathological conditions. We previously showed that fibroblast growth factor 2 (FGF2) upregulates the expression and activity of the enzymes ecto-5′-nucleotidase (CD73) and adenosine deaminase (ADA). Here, we further demonstrate that this occurs in concentration- and time-dependent manners in cultured rat spinal cord astrocytes and is suppressed by inhibitors of the FGF receptor as well as the mitogen-activated protein kinases (MAPKs). We also found that FGF2 increased the phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK, leading to the increased expression and activity of CD73 and ADA. Our findings reveal the involvement of FGF2/MAPK pathways in the regulation of purine metabolic enzymes in astrocytes. These pathways may contribute to the control of extracellular purine concentrations under physiological and pathological conditions.

三磷酸腺苷 (ATP) 和腺苷是中枢神经系统中的神经递质和神经调节剂。星形胶质细胞通过 ATP 释放调节胞外嘌呤浓度，并通过胞外酶调节其代谢。星形胶质细胞中嘌呤代谢酶的表达和活性在病理条件下增加。我们之前表明，成纤维细胞生长因子 2 (FGF2) 上调 ecto-5'-核苷酸酶 (CD73) 和腺苷脱氨酶 (ADA) 的表达和活性。在这里，我们进一步证明，这在培养的大鼠脊髓星形胶质细胞中以浓度和时间依赖性方式发生，并且被 FGF 受体抑制剂和丝裂原活化蛋白激酶 (MAPK) 抑制。我们还发现 FGF2 增加了 MAPKs 的磷酸化，包括细胞外信号调节激酶、c-Jun N 端激酶和 p38 MAPK，导致 CD73 和 ADA 的表达和活性增加。我们的研究结果揭示了 FGF2/MAPK 通路参与星形胶质细胞中嘌呤代谢酶的调节。这些途径可能有助于在生理和病理条件下控制细胞外嘌呤浓度。