BIO-AND IMMUNO-CHEMICAL STUDIES ON OPIATE RECEPTORS

阿片受体的生物和免疫化学研究

• 批准号: 3211714
• 负责人: JAY A GLASEL
• 金额: $ 9.55万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211714
• 关键词: antiidiotype antibody; chemical binding; conformation; gene expression; genetic recombination; histochemistry /cytochemistry; immunochemistry; laboratory mouse; laboratory rat; neuropeptide receptor; protein sequence

The purpose of this research is to combine the expertise of two laboratories in fundamental studies on the biochemistry and molecular biology of opiate receptors. Our laboratory has developed an immunochemical approach towards characterizing the receptors. In particular, this has involved the production of anti-idiotypic antibodies which competitively inhibit drug binding to the receptors. The other laboratory has been one of the world leaders in developing solubilization methods which are applicable to these particular membrane bound receptors. Anti-idiotypic antibodies which bind specifically to opiate receptors are to be used as probes in biochemical, molecular biological and immunocytological studies on opiate receptors. In the biochemical work the antibodies will be used in conjunction with reversible protein-protein cross-linking agents in order to solublize the entire receptor complexes. These will then be purified using immunoaffinity techniques in order to obtain receptor complexes which may be studied both in their entirtey as well as broken into their components for detailed characterization. In molecular biological work the anti-idiotypic antibodies will be used as probes for translational products in recombinant DNA experiments. With these techniques opiate receptor proteins will be sequenced indirectly. This information will be further used, in a second stage of the work, to sequence the genomic arrangements which give rise to the receptors. The immunocytological work will be directed towards exploring methods directed towards the end of fractionating opiate receptor-bearing neurons from the general population of central nervous tissue neurons. This latter, combined with the molecular biological information will ultimately lead to studies of; the control of opiate receptor expression in cells, the primary events following ligand recognition by the receptors, and the roles of receptors in pain path-ways and addictive liability of drugs.

本研究的目的是联合收割机的专业知识， 生物化学基础研究实验室， 阿片受体的分子生物学 本实验室 开发了一种免疫化学方法， 受体。 特别是，这涉及生产 竞争性抑制药物结合的抗独特型抗体 到受体。 另一个实验室是世界上 在开发适用的增溶方法方面的领导者 这些特定的膜结合受体。 特异性结合阿片类药物的抗独特型抗体 受体将被用作生物化学、分子生物学和生物医学领域的探针。 阿片受体的生物学和免疫细胞学研究。 在 抗体的生化工作将与 与可逆的蛋白质-蛋白质交联剂， 溶解整个受体复合物。 这些将是 使用免疫亲和技术纯化以获得 受体复合物，可以研究其整体， 并将其分解为各个组件， 特征化 在分子生物学工作中， 抗体将用作翻译产物的探针， 重组DNA实验。 通过这些技术， 受体蛋白将被间接测序。 这些信息 将在工作的第二阶段进一步用于排序 产生受体的基因组排列。 的 免疫细胞学工作将致力于探索 针对阿片剂分馏终点的方法 受体承载神经元从一般人口的中央 神经组织神经元 后者，结合分子 生物信息最终将导致研究; 控制细胞中阿片受体的表达， 在受体识别配体后， 疼痛通路中的受体和药物的成瘾性。