Rathbone M P, Christjanson L, Deforge S, Deluca B, Gysbers J W, Hindley S, Jovetich M, Middlemiss P, Takhal S
Department of Biomedical Sciences, McMaster University Health Science Centre, Hamilton, Ontario, Canada.
Med Hypotheses. 1992 Apr;37(4):232-40. doi: 10.1016/0306-9877(92)90193-g.
Extracellular purine nucleosides and nucleotides are ubiquitous, phylogenetically ancient, intercellular signals. Purines are released from hypoxic, damaged or dying cells. Purine nucleosides and nucleotides are potent mitogens for several types of cells such as fibroblasts, endothelial cells and neuroglia. They also induce other cell types to differentiate. For example, they act synergistically with nerve growth factor to stimulate neurite outgrowth from a pheochromocytoma cell line (PC12). We propose that after injury to tissues, including the central nervous system, purine nucleosides and nucleotides interact synergistically with other growth factors. They stimulate proliferation and morphological changes in the various cell types involved in the wound healing response. In the central nervous system this response includes glial proliferation, capillary endothelial cell proliferation, and sprouting of nerve axons. Since many actions of extracellular purines are mediated through specific cell surface receptors, this hypothesis has broad pharmacological implications.
细胞外嘌呤核苷和核苷酸广泛存在，在系统发育上古老，是细胞间信号。嘌呤从缺氧、受损或濒死的细胞中释放。嘌呤核苷和核苷酸是几种类型细胞（如成纤维细胞、内皮细胞和神经胶质细胞）的强效促有丝分裂原。它们还诱导其他细胞类型分化。例如，它们与神经生长因子协同作用，刺激嗜铬细胞瘤细胞系（PC12）的神经突生长。我们提出，在包括中枢神经系统在内的组织损伤后，嘌呤核苷和核苷酸与其他生长因子协同相互作用。它们刺激参与伤口愈合反应的各种细胞类型的增殖和形态变化。在中枢神经系统中，这种反应包括神经胶质细胞增殖、毛细血管内皮细胞增殖和神经轴突发芽。由于细胞外嘌呤的许多作用是通过特定的细胞表面受体介导的，这一假设具有广泛的药理学意义。
