MOLECULAR STUDY OF GABA & BENZODIAZEPINE RECEPTOR

GABA 的分子研究

• 批准号: 3564447
• 负责人: JOHN F. TALLMAN
• 金额: $ 19.67万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3564447
• 关键词: GABA receptor; affinity labeling; antidepressants; benzodiazepine receptor; benzodiazepines; developmental neurobiology; dopamine receptor; histochemistry /cytochemistry; immunochemistry; laboratory mouse; laboratory rat; membrane channels; membrane reconstitution /synthesis; messenger RNA; monoclonal antibody; neuropharmacology; neurotransmitter metabolism; nucleic acid probes; radioimmunoassay; radiotracer; tissue /cell culture; tranquilizer

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.

本研究的长期目标是了解 苯并二氮杂卓类及相关药物作用的分子基础 作用于GABA/苯并二氮杂卓受体复合物的化合物。 这些药物是最广泛的处方化合物， 治疗焦虑和睡眠障碍。 它们也被用于 作为抗癫痫药。 本建议中采用的方法 分离出GABA的蛋白质 苯二氮卓受体复合物，制备这些抗体 蛋白质和识别蛋白质的生物化学和 免疫细胞化学 此外，分子探针， GABA/苯二氮卓受体和其他δ β亚单位 受体分子正在制备中，以识别培养的 从细胞和组织中提取这些受体。 之间的匹配 mRNA的合成和受体数量， 受体合成被诱导，并且在发育过程中， 研究了 长期服用抗焦虑药和 抗抑郁药对受体动力学的影响将通过比较 mRNA和受体合成。 用于mRNA的技术 用北方印迹法测定mRNA水平， 用放射性标记的探针定量。 这样，一个清晰的 受体转换和药物作用之间的关系将是 确立了习 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 抑郁症将被检查。