Abstract
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.
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This work was supported by JSPS KAKENHI (grant number JP19K23701) and the Naito Foundation.
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Eguchi, R., Kitano, T. & Otsuguro, Ki. Fibroblast growth factor 2 upregulates ecto-5′-nucleotidase and adenosine deaminase via MAPK pathways in cultured rat spinal cord astrocytes. Purinergic Signalling 16, 519–527 (2020). https://doi.org/10.1007/s11302-020-09731-0
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DOI: https://doi.org/10.1007/s11302-020-09731-0