MOLECULAR BIOLOGY OF OPIOID MEMBRANE RECEPTORS

提出的关于发现多个 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月离职。在那之前 时间，积累的证据有力地表明大脑 二倍体硬骨鱼Mummichog的基因包含两个截然不同的转录本 对于每一种阿片受体，分别是Delta、Mu和Kappa。部分 序列分析表明，它们之间的差异更大 而不是与人类受体基因的同源性。这些 结果应该完成，因为它们清楚地揭示了 药理上不同的受体亚型 存在于独特的蛋白质分子中。另一个项目涉及一个 研究人多药耐药-1可能参与的模型系统 (多药耐药蛋白-1)在多肽的传递中 利用稳定表达的基因构建难治性血脑屏障 转化成成纤维细胞系。事实上，观察到了一种相关性 一系列N-和C-末端的疏水性之间 含有DMT-Tic的改良型Delta-阿片拮抗剂 药效团及其抑制该酶活性的能力 膜结合蛋白。这些数据应该会增强我们的知识 用于设计新的阿片类似物治疗人类 毒瘾、酒精依赖和免疫抑制。

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.