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.

关于发现多个 阿片受体的染色体转录本终止于 1998年6月，我们的博士后离开了。直到那 随着时间的推移，越来越多的证据表明， Mummichog，一种二倍体硬骨鱼，包含两个不同的转录本， 对于每一种阿片受体，δ，μ和κ。部分 序列分析表明，它们在很大程度上不同 而不是与人受体cDNA的相互作用。这些 结果应该完成，因为它们清楚地阐明了 不同的受体亚型 存在于独特的蛋白质分子中。另一个项目涉及 用于研究人MDR-1的可能参与的模型系统 （多药耐药蛋白-1）在肽通过 顽固性血脑屏障利用稳定转染的cDNA 转化成纤维细胞系事实上， 一系列N-和C-末端的疏水性之间 含有Dmt-Tic的修饰的δ-阿片样物质拮抗剂 药效团及其抑制这种活性的能力 膜结合蛋白。这些数据应该能让我们 用于设计新的阿片类药物类似物治疗人类 吸毒、酗酒和免疫抑制。