SELECTIVE FLUORESCENT PROBES FOR OPIOID RECEPTOR TYPES

用于阿片受体类型的选择性荧光探针

• 批准号: 2120949
• 负责人: PHILIP S PORTOGHESE
• 金额: $ 12.01万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120949
• 关键词: analog; chemical synthesis; confocal scanning microscopy; fluorescent dye /probe; guinea pigs; high performance liquid chromatography; indoles; laboratory mouse; ligands; method development; naltrexone; narcotic antagonists; opioid receptor; receptor binding; smooth muscle; thin layer chromatography

The long-term goal of this research is to develop selective, fluorescent probes for delta, kappa, and mu opioid receptor types. The probes will be designed so that functioning opioid receptors can be visualized using the confocal scanning laser microscope. This goal will be pursued by the use of selective pharmacopheres derived from naltrindole (delta), norbinaltorphimine (kappa), and oxymorphone and naltrexone (mu). Three different colored fluorophores will be attached to the pharmacophores through strategically placed hydrophilic spacers so that affinity, selectivity, and potency of the ligands are retained. The different colored fluorophores will be employed in an effort to ultimately image three opioid receptor types simultaneously. These ligand will be evaluated in four in vitro preparations: binding in guinea pig brain membranes, antagonist and agonist potencies in the guinea pig ileum and mouse vas deferens, and confocal microscopic visualization in three cell populations (NGl08-l5, SH-SY5Y, guinea pig cerebellum) that contain defined opioid receptor populations. Promising ligands will then undergo antinociceptive testing and, ultimately, neural tissues from the tested animals will be examined to evaluate the ability of the probe to image opioid receptor populations in vivo. The attainment of this long-range goal will afford an armamentarium of selective opioid receptor probes for scanning laser confocal microscopy.

这项研究的长期目标是开发选择性，荧光 δ、κ和μ阿片受体类型的探针。探测器将在 设计成可以使用 共聚焦激光扫描显微镜这一目标将通过使用 来自纳曲吲哚（δ）的选择性药效团， norbinaltorphimine（kappa）和羟吗啡酮和纳洛酮（mu）。三 不同颜色的荧光团将附着在药效团上 通过策略性地放置亲水间隔物， 保留了配体的选择性和效力。不同 彩色荧光团将被用于最终成像 三种阿片受体同时存在将对这些配体进行评价 在四种体外制备中：在豚鼠脑膜中的结合， 豚鼠回肠和小鼠血管中的拮抗剂和激动剂效力 输精管，共聚焦显微镜可视化在三个细胞群体 （NG 108 - 15，SH-SY 5 Y，豚鼠小脑） 受体群体有希望的配体将经历抗伤害感受 测试，并最终，神经组织从测试的动物将是 检查以评价探针成像阿片受体的能力 体内的种群。实现这一长远目标将为 选择性阿片受体激光扫描探针设备 共聚焦显微镜