MODULATION OF ASTROGLIAL CELL-PROLIFERATION BY ANALOGS OF ADENOSINE AND ATP IN PRIMARY CULTURES OF RAT STRIATUM
MODULATION OF ASTROGLIAL CELL-PROLIFERATION BY ANALOGS OF ADENOSINE AND ATP IN PRIMARY CULTURES OF RAT STRIATUM
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DOI：
10.1016/0306-4522(94)90099-x
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发表时间：
1994-03-01
期刊：
影响因子：
3.3
通讯作者：
BURNSTOCK, G
中科院分区：
文献类型：
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作者：
ABBRACCHIO, MP;SAFFREY, MJ;BURNSTOCK, G
我们已经研究了可能的嘌呤受体介导的调制星形胶质细胞增殖的神经元胶质细胞的原代培养从大鼠纹状体。培养物在2-氯-腺苷或α-β-亚甲基-ATP（分别作为腺苷/ P1和ATP/P2嘌呤受体的激动剂）存在下生长3天，然后用胶质细胞酸性蛋白的抗体进行免疫染色。2-氯-腺苷减少和α-β-亚甲基-ATP增加培养中的星形胶质细胞的数量。对于这两种衍生物，其作用均呈剂量依赖性。α-β-亚甲基-ATP的作用被锥虫苷苏拉明P-拮抗，表明苏拉明敏感的P2嘌呤受体的参与，而2-氯-腺苷的作用不被逆转的P1嘌呤受体拮抗剂对磺酰基-苯基-茶碱，这意味着黄嘌呤不敏感的腺苷嘌呤受体亚型的激活。为了评估这两种类似物存在下星形胶质细胞增殖的程度，将一些培养物与溴脱氧尿苷一起孵育24 h后固定，然后对胶质细胞酸性蛋白和溴脱氧尿苷进行双重免疫染色。结果表明，两种嘌呤均能以相反的方式调节星形胶质细胞，分别通过激活P1和P2嘌呤受体来诱导细胞数量的减少或增加。对于P2嘌呤受体介导的作用，溴脱氧尿苷阳性星形胶质细胞的百分比和细胞数量之间存在定量相关性。对于P1嘌呤受体介导的效应，这两个参数之间没有明显的相关性，这表明激活的独立效应，涉及其他机制，除了刺激DNA合成，并最终导致细胞数量的减少。这些研究结果在体内调节星形胶质细胞的功能，以及在创伤和缺血相关的胶质增生的可能相关性进行了讨论。
We have studied the possible purinoceptor-mediated modulation of astroglial cell proliferation in neuron-glia primary cultures obtained from rat corpus striatum. Cultures were grown for three days in the presence of either 2-chloro-adenosine or alpha beta-methylene-ATP (which behave as agonists of adenosine/ P1 and ATP/P2 purinoceptors, respectively), and then immunostained with an antibody to glial fibrillary acidic protein. 2-Chloro-adenosine decreased and alpha beta-methylene-ATP increased the number of astroglial cells in culture. For both derivatives, the effect was dose-dependent. The effect of alpha beta-methylene-ATP was p-antagonized by the trypanoside suramin, suggesting the involvement of a suramin-sensitive P2 purinoceptor, whereas the effect of 2-chloro-adenosine was not reversed by the P1 purinoceptor antagonist p-sulphonyl-phenyl-theophylline, implying the activation of a xanthine-insensitive adenosine purinoceptor subtype. In order to evaluate the extent of astrocyte proliferation in the presence of these two analogues, some cultures were incubated with bromodeoxyuridine for 24 h before fixing, and then double-immunostained for glial fibrillary acidic protein and bromodeoxyuridine. The percentage of bromodeoxyuridine positive astrocytes was significantly increased after exposure to both agents.It is therefore concluded that purines can modulate astroglial cells in opposite ways, inducing decreases or increases of cell number by activation of P1 and P2 purinoceptors, respectively. For the P2 purinoceptor-mediated effect, there was a quantitative correlation between the percentage of bromodeoxyuridine positive astrocytes and the cell number. For the P1 purinoceptor-mediated effect, no apparent correlation between these two parameters was found. This suggests the activation of independent effects, which involve other mechanisms besides the stimulation of DNA synthesis, and which eventually result in a reduction of cell number. The possible relevance of these findings to in vivo regulation of astrocyte cell function as well as in trauma- and ischaemia-associated hypergliosis is discussed.