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: 6237944
• 负责人: PHILIP S PORTOGHESE
• 金额: $ 8.62万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-10 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6237944
• 关键词: analgesia; cerebellum; chemical synthesis; confocal scanning microscopy; drug design /synthesis /production; drug receptors; epididymis; fluorescent dye /probe; guinea pigs; ileum; infrared spectrometry; laboratory mouse; ligands; mass spectrometry; membrane proteins; molecular site; naltrexone; narcotic antagonists; nuclear magnetic resonance spectroscopy; opioid receptor; protein structure; receptor binding; smooth muscle; stimulant /agonist; tissue /cell culture

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 pharmacophores derived from naltrindole (delta), norbinaltorphimine (kappa), and oxymorphone and naltrexone (mu). Three different colored fluorephores 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 fluorephores will be employed in an effort to ultimately image three opioid receptor types simultaneously. These ligands 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 (NG108-15, 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 on 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的、荧光的 探测Delta、kappa和u阿片受体类型。探测器将会 被设计成功能阿片受体可以用 共聚焦扫描激光显微镜。这一目标将由 使用从纳曲哚(Delta)衍生的选择性药效团， 去甲肾上腺素(Kappa)、羟吗啡酮和纳曲酮(Mu)。三 不同颜色的荧光粉将附着在药效团上 通过有策略地放置亲水性间隔物， 保留了配体的选择性和有效性。不同的 彩色荧光将被用来努力最终成像 三种阿片受体类型同时发生。这些配体将是 四种体外制剂的评价：豚鼠脑结合 豚鼠回肠膜、拮抗剂和激动剂的作用 小鼠输精管三种细胞的共聚焦显微镜观察 种群(NG108-15、SH-SY5Y、豚鼠小脑)含有 已定义的阿片受体群体。有希望的配体随后将经历 抗伤害性测试，最终，从受试者的神经组织 将对动物进行检查，以评估探测器成像的能力 体内的阿片受体种群。实现这一长远目标 Goal将负担起对阿片受体选择性探针的研究 扫描激光共聚焦显微镜。