MOLECULAR STUDY OF GABA & BENZODIAZEPINE RECEPTOR

这项研究的长期目标是了解 苯二氮卓类及其相关化合物作用的分子基础 作用于GABA/苯二氮卓类受体复合体的化合物。 这些药物是最广泛使用的处方化合物之一 治疗焦虑和睡眠障碍。它们也被用来 作为抗癫痫药。该提案中使用的方法具有 一直在分离属于GABA一部分的蛋白质- 苯二氮卓类受体复合体的制备 蛋白质，并对蛋白质进行生化和鉴定 免疫细胞化学。此外，分子探针到和 GABA/苯二氮卓类受体的β-亚基等 正在准备受体分子来识别培养的 从细胞和组织中获取这些受体。这场比赛的对手是 基因合成与受体数目的关系 受体的合成是被诱导的，在发育过程中 学习。慢性服用抗焦虑药物的疗效观察 抗抑郁药对受体动力学的影响将通过比较研究 信使核糖核酸和受体合成。信使核糖核酸的检测技术 检测结果为Northern印迹法，mRNA水平为 用放射性标记的探针进行定量。这样一来，一种清晰的 受体周转和药物作用之间的关系将是 已经成立了。这些变化与治疗的相关性 这些药物的作用及其在焦虑症和 我们将对抑郁症进行检查。

The long-term objectives of this research are to understand the molecular basis of the actions of benzodiazepines and related compounds which act at the GABA/benzodiazepine receptor complex. These drugs are among the most widely prescribed compounds for the treatment of anxiety and sleep disturbances. They are also used as antiepileptic agents. The approach used in this proposal has been to isolate the proteins which are part of the GABA- benzodiazepine receptor complex, prepare antibodies to these proteins and identify the proteins biochemically and immunocytochemically. In addition, molecular probes to the and delta beta subunits of GABA/benzodiazepine receptor and other receptor molecules are being prepared to identify mRNA in cultured cells and from tissue for these receptors. The match between synthesis of mRNA and receptor number under conditions where receptor synthesis is induced and during development is to be studied. The effect of chronic administration of anxiolytics and antidepressants on receptor dynamics will be studied by comparing mRNA and receptor synthesis. The techniques to be used for mRNA determination are northern blotting and the levels of mRNA are quantitated with radiolabeled probes. ln this way, a clear relationship between receptor turnover and drug action will be established. The correlation of these changes with the therapeutic action of these drugs and their use in anxiety disorders and depression will be examined.