CANNABINOID RECEPTOR PHARMACOLOGY AND BIOCHEMISTRY

δ-9-四氢大麻酚（δ-9 THC）是CNS的主要活性物质， 大麻的成分 大麻类药物，包括 去乙酰左南曲多和CP-55940，有效模拟 delta-9 THC在一些动物模型中的作用 利用这些强效大麻素 化合物，我的实验室确定， 的CNS活性大麻素药物是通过抑制腺苷酸环化酶， G 我们放射性标记CP-55940，并开发了受体结合试验， 大麻素受体的生物化学特征。 这项工作将继续实现以下目标： 1. 大麻素的细胞调节的表征 神经元细胞中的受体，包括合成、翻译后 加工、转运至质膜和潜在的隔离 响应于慢性激动剂刺激; 2.大麻素结构特性的表征 受体和功能性伴随物的测定; 3.大麻素受体的纯化及其用途 蛋白质结构分析、抗体生产、重组 信号转导G蛋白和纯化内源性 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CNS中，并且纯化和表征 在大麻素受体上负责这种作用的因子。 产生用于内源性大麻素样结合的抗体 因子和免疫测定的发展。

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.