Abstract
Proliferation of brain astrocytes as a result of cell death has been well documented in vivo. Dying cells release purine and pyrimidine nucleosides and nucleβotides and their deoxy derivatives both from soluble intracellular pools and from DNA and RNA. Previously, we have observed that purine nucleosides and nucleotides stimulate chick astrocyte proliferation in vitro. To further our analysis, we questioned whether pyrimidines or the deoxy derivatives of purine nucleosides and nucleotides might also be astrocyte mitogens. Pyrimidine nucleosides, nucleotides, and their deoxynucleotide derivatives were uniformly inactive. In contrast, deoxyguanosine, deoxyadenosine, and their monoβ, diβ, and triphosphates stimulated thymidine incorporation into astrocytes at concentrations similar to those at which their ribonucleoside and ribonucleotide analogues were active. Inosine, IMP, ITP, and hypoxanthine were active, whereas xanthine and xanthosine were not. However, XMP, XDP, and XTP stimulated thymidine incorporation. The effects of the nucleosides and deoxynucleosides were inhibited by antagonists of adenosine A~2~ receptors. These data indicate that most purine nucleosides, deoxynucleosides, and their 5β² mono, diβ, and triphosphate derivatives released from damaged cells are capable of stimulating astrocyte proliferation in vitro and may contribute to astrocyte proliferation in vivo following injury to the CNS.