CANNABINOID RECEPTOR PHARMACOLOGY AND BIOCHEMISTRY

大麻素受体药理学和生物化学

• 批准号: 2116067
• 负责人: ALLYN C HOWLETT
• 金额: $ 9.84万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2116067
• 关键词: G protein; adenylate cyclase; analgesics; antibody formation; biological signal transduction; brain metabolism; cannabinoids; drug receptors; enzyme inhibitors; laboratory rat; neuropharmacology; phenanthridines; posttranslational modifications; protein purification; receptor binding; tissue /cell culture

Delta-9-Tetrahydrocannabinol(delta-9 THC)is the primary CNS-active component of Cannabis sativa. Cannabinoid analgetics, including desacetyllevonantradol and CP-55940, potently mimic the effects of delta-9 THC in a number of animal models. Using these potent cannabinoid compounds, my laboratory determined that the cellular mechanism of action of the CNS-active cannabinoid drugs was to inhibit adenylate cyclase via G-i. We radiolabeled CP-55940 and developed a receptor binding assay to biochemically characterize the cannabinoid receptor. This work will continue with the following goals: 1. Characterization of the cellular regulation of the cannabinoid receptor in neuronal cells including synthesis, post-translational processing, transit to the plasma membrane, and potential sequestration in response to chronic agonist stimulation; 2. Characterization of the structural properties of the cannabinoid receptor and determination of the functional concomitants; 3. Purification of the cannabinoid receptor and use of the purified protein for structure analysis, antibody production, reconstitution with signal transducing G-proteins and to purify an endogenous cannabinoid-like binding activity for the cannabinoid receptor. 4. Identification of an endogenous cannabinoid-like binding activity present in the CNS, and purification ana characterization of the factor(s) responsible for this action at the cannabinoid receptor. Production of antibodies for the endogenous cannabinoid-like binding factor(s) and development of immunoassays.

Delta-9-四氢大麻酚（Delta-9 THC）是主要的CNS活性 大麻萨氏菌的组成部分。 大麻素肛门型，包括 Deacetyllevonantradol和CP-55940，有效地模仿 许多动物模型中的delta-9 THC。 使用这些有效的大麻素 化合物，我的实验室确定了动作的细胞机理 CNS活性大麻素药物是通过 G-i。 我们放射标记的CP-55940，并开发了一种受体结合测定 生化表征大麻素受体。 这项工作将继续以下目标： 1。大麻素细胞调节的表征 神经元细胞中的受体，包括合成，翻译后的受体 加工，到质膜的过渡和电势隔离 响应慢性激动剂刺激； 2。大麻素的结构特性的表征 受体和功能伴随的确定； 3。大麻素受体的纯化和纯化的使用 蛋白质用于结构分析，抗体生产，重建 信号转导G蛋白并纯化内源性 大麻素受体的大麻素样结合活性。 4。鉴定内源性大麻素样结合活性 中枢神经系统中存在，并纯化 在大麻素受体上负责此作用的因子。 产生内源性大麻素样结合的抗体 因素和免疫测定的发展。