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.

三角洲-9-四氢大麻酚(Delta-9-THC)是中枢神经系统的主要活性物质 大麻的主要成分。大麻类止痛药，包括 去乙酰左旋氨曲醇和CP-55940有效地模拟了 Delta-9 THC在一些动物模型中的应用。使用这些强效大麻素 化合物，我的实验室确定了细胞的作用机制 中枢神经系统活性大麻类药物中的一种是通过抑制腺苷环化酶 G-I。我们对CP-55940进行了放射性标记，并建立了受体结合试验 对大麻素受体进行生物化学表征。 这项工作将继续实现以下目标： 1.大麻素的细胞调控特性 神经细胞中的受体，包括合成、翻译后 加工，转移到质膜，和潜在的隔离 对慢性激动剂刺激的反应； 2.大麻素的结构性质表征 受体及其功能伴生体的测定； 3.大麻素受体的纯化及其用途 用于结构分析、抗体生产、重组的蛋白质 信号转导G蛋白和提纯内源性 大麻素受体的大麻素样结合活性。 4.内源性大麻素样结合活性的鉴定 存在于中枢神经系统中，并对其纯化和鉴定 负责大麻素受体这一作用的因素(S)。 内源性类大麻素样结合抗体的制备 因子(S)与免疫分析的发展。