Bruce J H, Ramirez A M, Lin L, Oracion A, Agarwal R P, Norenberg M D
Department of Pathology, University of Miami, FL.
Brain Res. 1991 Nov 8;564(1):167-70. doi: 10.1016/0006-8993(91)91369-c.
Peripheral-type benzodiazepine (BZD) receptors have been identified in brain and are predominantly localized to astrocytes. To determine their potential role in controlling astroglial proliferation, DNA synthesis, growth curves and mitotic index were investigated in primary astrocyte cultures which had been exposed to Ro5-4864 (a peripheral-type BZD ligand) and PK11195 (a peripheral-type BZD receptor antagonist). There was a dose-dependent inhibition of mitosis when two-week-old cells in culture were exposed to 50 nM, 500 nM, 1 microM and 10 microM Ro5-4864 for 24 h. Exposure of 5-, 8-, 12- and 15-day-old cultures to Ro5-4864 and PK11195 for 24 h did not affect growth rate and DNA synthesis; however, continuous exposure to 10 microM Ro5-4864 caused a persistent inhibition of cell growth and [3H]thymidine incorporation (P less than 0.05) while nanomolar concentrations did not cause any significant change. Concurrent administration of Ro5-4864 with PK11195 resulted in a partial reversal of Ro5-4864-induced inhibition in DNA synthesis and mitosis. These results indicate that peripheral-type BZDs are capable of inhibiting proliferation of astrocytes in culture.
外周型苯二氮䓬（BZD）受体已在大脑中被鉴定出来，且主要定位于星形胶质细胞。为了确定它们在控制星形胶质细胞增殖中的潜在作用，我们在原代星形胶质细胞培养物中研究了DNA合成、生长曲线和有丝分裂指数，这些培养物已暴露于Ro5 - 4864（一种外周型BZD配体）和PK11195（一种外周型BZD受体拮抗剂）。当培养两周的细胞暴露于50 nM、500 nM、1 μM和10 μM的Ro5 - 4864 24小时时，有丝分裂受到剂量依赖性抑制。将5天、8天、12天和15天的培养物暴露于Ro5 - 4864和PK11195 24小时并不影响生长速率和DNA合成；然而，持续暴露于10 μM的Ro5 - 4864会导致细胞生长和[³H]胸腺嘧啶核苷掺入持续受到抑制（P小于0.05），而纳摩尔浓度则不会引起任何显著变化。Ro5 - 4864与PK11195同时给药导致Ro5 - 4864诱导的DNA合成和有丝分裂抑制部分逆转。这些结果表明外周型BZDs能够抑制培养的星形胶质细胞的增殖。
