Barochovsky O, Patel A J
Neurochem Res. 1982 Sep;7(9):1059-74. doi: 10.1007/BF00964886.
The role in the regulation of cell replication of the neurotransmitter compounds and the drugs which affect their balance was studied in vitro, using morphologically preserved brain slices. Compounds affecting noradrenergic, dopaminergic and serotoninergic neurotransmitter systems reduced the brain cell replication, measured in terms of the rate of [3H]thymidine incorporation into DNA. The reduction was dose dependent and half-maximal effects were obtained at about 1-5 x 10(-4) M concentrations. Although agonists and antagonists both showed similar inhibitory effect, the action of agonists was reversed by the appropriate antagonists. Also, the pharmacologically active isomers were several-fold more effective than the inactive isomers in forebrain slices, although with cerebellar slices the selectivity was less marked. Cyclic nucleotides and drugs affecting cholinergic neurotransmitter systems were apparently ineffective. These results indicate that monoamines may be involved in the regulation of cell replication in the developing brain. Furthermore, as some of the CNS acting drugs tested are suspected behavioural teratogens the present results suggest that the reported behavioural abnormalities in the offspring may be related, in part, to a chronologically determined interference with the formation of certain cell types.
利用形态学上保存完好的脑切片，在体外研究了神经递质化合物及影响其平衡的药物在细胞复制调节中的作用。影响去甲肾上腺素能、多巴胺能和5-羟色胺能神经递质系统的化合物可降低脑细胞复制，这是通过[3H]胸腺嘧啶核苷掺入DNA的速率来衡量的。这种降低呈剂量依赖性，在约1-5×10（-4）M浓度时可获得半数最大效应。虽然激动剂和拮抗剂均显示出相似的抑制作用，但激动剂的作用可被相应的拮抗剂逆转。此外，在前脑切片中，药理活性异构体的效力比无活性异构体高几倍，不过在小脑切片中这种选择性不太明显。环核苷酸及影响胆碱能神经递质系统的药物显然无效。这些结果表明，单胺可能参与发育中大脑的细胞复制调节。此外，由于所测试的一些中枢神经系统作用药物被怀疑是行为致畸剂，目前的结果表明，所报道的后代行为异常可能部分与按时间顺序确定的对某些细胞类型形成的干扰有关。
