Huffaker T, Corcoran T, Wagner J A
J Cell Physiol. 1984 Aug;120(2):188-96. doi: 10.1002/jcp.1041200212.
Low concentrations (10-50 microM) of adenosine (EC50 = 17 microM) or chloroadenosine (EC50 = 23 microM) prevent the division of PC12 cells. This inhibition is not mimicked by guanosine, inosine, 3',5' dideoxyadenosine, phenylisopropyladenosine, or adenylylimidodiphosphate. The growth inhibition is not relieved by addition of uridine or deoxycytidine, nor is it potentiated by homocysteine thiolactone. Inhibition of adenosine uptake does not inhibit adenosine-dependent growth arrest. PC12 variants that are deficient in adenosine kinase are as sensitive as wild-type cells to the growth-inhibitory effects of adenosine. These experiments suggest that adenosine prevents cell division at an adenosine receptor rather than acting after being metabolically altered. The adenosine receptor that inhibits cell division does not appear to be the adenosine receptor that stimulates adenylate cyclase for these reasons: (1) phenylisopropyladenosine, which is a potent agonist of this receptor, does not inhibit cell division; (2) 3',5' dideoxyadenosine does not antagonize the effect of adenosine on cell division; and (3) theophylline does not affect growth inhibition by adenosine. Thus, these experiments suggest the existence of a second adenosine receptor that can inhibit cell division. Adenosine also promotes the morphological differentiation of PC12 cells. In the presence of the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenosine (EHNA), adenosine causes the formation of short neurites (one-half to one and one-half cell diameters in length). Adenosine also increases the rate of neurite formation of both long and short neurites in response to NGF.
低浓度（10 - 50微摩尔）的腺苷（半数有效浓度[EC50] = 17微摩尔）或氯腺苷（EC50 = 23微摩尔）可阻止PC12细胞分裂。鸟苷、肌苷、3',5'-二脱氧腺苷、苯异丙基腺苷或腺苷酰亚胺二磷酸不会模拟这种抑制作用。添加尿苷或脱氧胞苷不能缓解生长抑制，同型半胱氨酸硫内酯也不会增强这种抑制作用。抑制腺苷摄取并不会抑制腺苷依赖性的生长停滞。腺苷激酶缺陷的PC12变体对腺苷的生长抑制作用与野生型细胞一样敏感。这些实验表明，腺苷是在腺苷受体处阻止细胞分裂，而不是在代谢改变后起作用。出于以下原因，抑制细胞分裂的腺苷受体似乎不是刺激腺苷酸环化酶的腺苷受体：（1）作为该受体强效激动剂的苯异丙基腺苷不会抑制细胞分裂；（2）3',5'-二脱氧腺苷不会拮抗腺苷对细胞分裂的作用；（3）茶碱不影响腺苷对生长的抑制作用。因此，这些实验表明存在第二种可抑制细胞分裂的腺苷受体。腺苷还可促进PC12细胞的形态分化。在腺苷脱氨酶抑制剂erythro-9-(2-羟基-3-壬基)腺苷（EHNA）存在的情况下，腺苷会导致短神经突的形成（长度为细胞直径的二分之一到一倍半）。腺苷还会增加PC12细胞对神经生长因子（NGF）产生的长、短神经突的神经突形成速率。
