Rathbone M P, Deforge S, Deluca B, Gabel B, Laurenssen C, Middlemiss P, Parkinson S
Department of Biomedical Sciences, McMaster University Health Science Centre, Hamilton, Ontario, Canada.
Med Hypotheses. 1992 Apr;37(4):213-9. doi: 10.1016/0306-9877(92)90190-n.
Extracellular purine nucleosides and nucleotides in micromolar concentrations stimulate proliferation of a variety of cell types in vitro and in vivo. As well they act synergistically with NGF to stimulate neurite outgrowth from PC12 cells. A variety of purine nucleosides and deoxyribonucleosides promote cell proliferation and increase intracellular cAMP. Their activities are inhibited by adenosine A2 receptor antagonists. Only adenosine interacts with the A2 receptor. We propose that the other nucleosides and deoxyribonucleosides inhibit extracellular adenosine deaminase, thereby increasing the extracellular concentration of adenosine. The nucleotides apparently act by stimulating P2y receptors coupled to inositol phosphate metabolism. We propose that the nucleosides and nucleotides act synergistically with other growth factors because each has distinct but complementary second messenger systems. If our hypotheses are correct, it should prove possible to modulate the growth and morphogenesis in several cell types using drugs that inhibit or stimulate adenosine A2 or purine P2y receptor agonists or the second messenger systems coupled to these receptors.
微摩尔浓度的细胞外嘌呤核苷和核苷酸在体外和体内均可刺激多种细胞类型的增殖。它们还与神经生长因子协同作用，刺激PC12细胞的神经突生长。多种嘌呤核苷和脱氧核糖核苷可促进细胞增殖并增加细胞内cAMP。它们的活性受到腺苷A2受体拮抗剂的抑制。只有腺苷与A2受体相互作用。我们认为，其他核苷和脱氧核糖核苷可抑制细胞外腺苷脱氨酶，从而增加细胞外腺苷的浓度。核苷酸显然是通过刺激与肌醇磷酸代谢偶联的P2y受体起作用的。我们认为，核苷和核苷酸与其他生长因子协同作用，因为它们各自具有独特但互补的第二信使系统。如果我们的假设正确，那么使用抑制或刺激腺苷A2或嘌呤P2y受体激动剂或与这些受体偶联的第二信使系统的药物，应该可以调节几种细胞类型的生长和形态发生。
