Differential expression, activity, and fibroblast growth factor 2-mediated modulation of purine-metabolizing enzymes...

Extracellular purines such as adenosine triphosphate and adenosine, serve as important neurotransmitters and modulators in the central nervous system. Extracellular purine concentrations are tightly regulated by a series of purine-metabolizing enzymes that convert adenosine triphosphate into adenosine and inosine. Both astrocytes and microglia, major glial cells in the central nervous system, contribute to extracellular purine metabolism; however, the differences in the expression profiles, enzymatic activities, and regulatory mechanisms of purine-metabolizing enzymes between these cells remain incompletely understood. In this study, we compared the expression levels and enzymatic activities of purine-metabolizing enzymes in cultured rat cortical astrocytes and microglia, and further examined their regulatory pathways. Microglia exhibited higher expression and activity of purine-metabolizing enzymes compared with astrocytes. Fibroblast growth factor 2 regulated the expression and activity of purine-metabolizing enzymes in astrocytes through pathways dependent on fibroblast growth factor receptors and mitogen-activated protein kinases, whereas such regulation was not observed in microglia. These findings highlight the pivotal role of microglia in central nervous system purine metabolism and suggest that fibroblast growth factor 2 modulates purine metabolism in a cell type-specific manner.