MOLECULAR BIOLOGY OF OPIOID MEMBRANE RECEPTORS

阿片类膜受体的分子生物学

• 批准号: 6106802
• 负责人: LAWRENCE H LAZARUS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6106802
• 关键词: endogenous opioid; membrane permeability; neuropharmacology; neurotransmitter agonist; neurotransmitter antagonist; opioid receptor; protein structure function; receptor expression; tissue /cell culture

The proposed project on the discovery of multiple chromosomal transcripts for opioid receptors was terminated with the departure of our postdoctoral fellow in June, 1998. Until that time, evidence accumulated which strongly suggested that the brain of Mummichog, a diploid teleost, contained two distinct transcripts for each of the opioid receptors, delta, mu and kappa. Partial sequence analyses indicated that they differed to a greater degree from each other than to that of the human receptor cDNA. These results should be completed as they clearly shed light on the possibility that the pharmacologically distinct receptor subtypes reside in unique protein molecules. Another project dealing with a model system for studying possible involvement of human MDR-1 (multi- drug resistance protein-1) in passage of peptides through the intractable blood-brain barrier utilized cDNA stably transfected into a fibroblast cell line. In fact, a correlation was observed between the hydrophobicity of a series of N- and C-terminally modified delta-opioid antagonists containing the Dmt-Tic pharmacophore and its ability to inhibit the activity of this membrane- bound protein. The data should enhance our knowledge for the design of new opioid analogues in the treatment of human of drug addiction, alcohol dependency and immunosuppression.

提议的关于发现多重的项目 阿片受体的染色体转录本用 我们的博士后研究员于1998年6月离开。 时间，积累的证据强烈建议大脑 二倍体遗产的木乃伊，包含两个不同的成绩单 对于每个阿片受体，三角洲，MU和Kappa。部分的 序列分析表明它们在更大程度上有所不同 彼此比人类受体cDNA的彼此相比。这些 结果应完成，因为它们明显地阐明了 药理学上不同受体亚型的可能性 驻留在独特的蛋白质分子中。另一个与 研究人类MDR-1可能参与的模型系统 （多耐药性蛋白1）在肽通过 使用的顽固性血脑屏障稳定转染了cDNA 进入成纤维细胞系。实际上，观察到相关性 在一系列N-和C末端的疏水性之间 经过修改的三角洲阿片类拮抗剂，其中包含DMT-TIC 药效团及其抑制其活性的能力 膜结合蛋白。数据应增强我们的知识 为了设计新的阿片类似类似物在治疗人类 吸毒，酒精依赖和免疫抑制。