SYNTHESIS OF PROBES TO MONITOR BRAIN RECEPTOR MOBILITY

监测脑受体迁移性的探针合成

• 批准号: 3504259
• 负责人: John L Neumeyer
• 金额: $ 5万
• 依托单位: SIGMA-ALDRICH RESEARCH BIOCHEMICAL
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3504259
• 关键词: Macaca mulatta; antiadrenergic agents; antiparkinson drugs; brain; chemical binding; chemical conjugate; chemical synthesis; dopamine; dopamine receptor; drug receptors; fluorescence microscopy; fluorescent dye /probe; lasers; ligands; neuropharmacology; neurotransmitters; photochemistry; radiotracer

Dysfunction of dopamine systems in the brain have been implicated in endocrine, neurological and psychiatric disorders, and dopaminergic drugs are widely prescribed for these disorders. Brain dopamine receptors are clearly implicated as the targets of these drugs. These receptors are in a mobile, dynamic state and can, be modulated by drugs, lesions, diseases, hormones and other challenges. For example, post-mortem brains of schizophrenic and Parkinson patients have altered levels of dopamine receptors, a consequence of dopamine drug therapies and/or the disease states. Although the end status of dopamine receptor modulation by drug treatment has been described, little is known about the cellular mechanism of drug-induced receptor adaptive processes. In Phase I of the project we propose to synthesize fluorescent probes as a novel approach to monitoring dopamine receptor mobility in brain membranes. Fluorescent compounds will be coupled to dopamine agonists (therapeutic drugs for Parkinson's disease) and antagonists (therapeutic agents for schizophrenia). We will test the affinity and selectivity of these compounds for dopamine receptors. Neural membranes at various levels of tissue organization will consequently be exposed to the fluorescent probe, photobleached by laser beam, and the recovery of fluorescence will be monitored by fluorescent microscopy. These compounds will provide much needed information on the mobility of dopamine occupied by therapeutic drugs.

大脑中多巴胺系统的功能障碍 与内分泌、神经和精神疾病有关， 并且多巴胺能药物被广泛用于这些疾病。 大脑多巴胺受体显然是 这些药物。 这些受体处于移动的动态状态， 可以通过药物、病变、疾病、激素和其他 挑战 例如，精神分裂症患者的死后大脑 帕金森患者的多巴胺受体水平发生了变化， 多巴胺药物治疗和/或疾病的结果 states. 虽然多巴胺受体调节的最终状态 通过药物治疗已经描述，关于药物治疗的知之甚少。 药物诱导的受体适应性过程的细胞机制。 在该项目的第一阶段，我们建议合成荧光 探针作为监测多巴胺受体的新方法 脑细胞膜的流动性。 荧光化合物将是 与多巴胺激动剂（帕金森氏症的治疗药物） 疾病）和拮抗剂（精神分裂症的治疗剂）。 我们将测试这些化合物的亲和力和选择性， 多巴胺受体 不同层次组织的神经膜 因此，组织将暴露于荧光 探针，用激光束光漂白，和恢复 通过荧光显微镜监测荧光。 这些 化合物将提供急需的信息， 多巴胺被治疗药物占据。