Patel A J, Béndek G, Balázs R, Lewis P D
Brain Res. 1977 Jul 1;129(2):283-97. doi: 10.1016/0006-8993(77)90008-7.
Reserpine, a well-known CNS depressant which depletes central monoamine stores, was found to produce in the brains of 11-day-old rats a severe depression in cell proliferation in terms of the rate of [3H]thymidine incorporation into DNA. The effect was studied in detail 12 h after ther administration of the drug (2.5 mg/kg, s.c.) when the rate of in vivo DNA synthesis in the forebrain was about one-third of control: the decrease was less marked in the cerebellum (rate about two-thirds of control). It was possible to exclude side effects of the drug, such as restricted food intake, hypothermia and an elevation of the level of blood corticosteroids being responsible for the reduction of [3H]thymidine incorporation into DNA. Kinetic studies showed that reserpine had no marked effect on the entry of [3H]thymidine from blood to brain, but it caused some retardation in the rate of [3H]thymidine conversion into [3H]thymidine nucleotides. Nevertheless, the severe depression of DNA labelling was evident even after correcting the values on the basis of [3H]thymidine nucleotide concentrations. In contrast to these effects, thymidine kinase activity was normal in the brain of reserpine-treated animals.
利血平是一种著名的中枢神经系统抑制剂,可耗尽中枢单胺类物质储备。研究发现,给11日龄大鼠注射利血平(2.5毫克/千克,皮下注射)12小时后,就[3H]胸腺嘧啶核苷掺入DNA的速率而言,其大脑中的细胞增殖出现严重抑制。给药时,前脑体内DNA合成速率约为对照的三分之一,小脑的下降幅度较小(速率约为对照的三分之二)。可以排除药物的副作用,如食物摄入量受限、体温过低和血液皮质类固醇水平升高导致[3H]胸腺嘧啶核苷掺入DNA减少。动力学研究表明,利血平对[3H]胸腺嘧啶核苷从血液进入大脑没有明显影响,但它导致[3H]胸腺嘧啶核苷转化为[3H]胸腺嘧啶核苷酸的速率有所减慢。然而,即使根据[3H]胸腺嘧啶核苷酸浓度校正数值后,DNA标记的严重抑制仍然明显。与这些效应相反,利血平处理动物的大脑中胸苷激酶活性正常。