ENDOGENOUS CANNABINOIDS AND BRAIN/IMMUNE FUNCTION

有令人信服的证据表明，在这两种情况下都存在内源性大麻素 大脑和免疫系统。两个G蛋白大麻素受体 都被克隆了。一种是在整个大脑中发现高浓度的，如 在一些外周组织中也是如此，而另一种则定位于 仅限于外围地区。金黄色葡萄球菌的分离鉴定 内源性大麻素，如阿南达胺，导致加强努力 了解内源性大麻素的功能意义。 对这些内源性配体的操纵应该揭示它们的功能 作用，尤其是通过大麻素受体介导，并导致 更好地了解大麻滥用的病因，查明 大麻素类药物的治疗用途，以及有害或有害的 或对免疫系统的保护作用。关于免疫系统的研究 是很重要的，因为它们可能允许通过以下方式连接机构 哪些内源性大麻素可以调节免疫功能。这样的调制 可能对免疫功能受损的人产生影响，特别是 艾滋病患者。抗肿瘤药物选择性拮抗剂的研究进展 大麻素受体亚型成为令人兴奋的新探索者 这些目标。这项提议的目的是继续这一点 多学科项目，包括五个研究项目和 一个行政核心，以定义内生的职能作用 大麻素。每一位私家侦探都是经验丰富的研究人员，他们会做出 独一无二的贡献。Mechoulam教授建议隔离和识别 其他调节花生胺活性的内源物质，如 以及进行一项综合计划。拉兹丹医生将继续他的 他将为以下目标提供新颖和创新的探测的综合计划 研究团队的其他成员。他的目标包括准备 稳定和高效的内源性物质类似物和 SR141716A的类似物。马丁博士和佩特威博士领导的研究小组将 进行内源性配体及其类似物的药理学评价 内源性激动剂和拮抗剂。这些组织还将使用这两个 耐受性发展与拮抗剂的可塑性探讨 受体和基因表达。马丁博士将解决依赖问题 阿南达胺的责任。卡明斯基博士建议建立 内源性配体对免疫系统的影响及阐明其天然作用 大麻素对免疫功能的影响。卡明斯基博士有证据表明 内源性配体对免疫细胞有不同的作用。这个 与会者已经证明了他们的合作努力 都是最有成效和成果的。

There is convincing evidence that endogenous cannabinoids exist in both the brain and the immune system. Two G-protein cannabinoid receptors have been cloned. one is found throughout the brain in high concentrations, as well as in several peripheral tissues, whereas the other is localized exclusively in the periphery. The isolation and identification of endogenous cannabinoids, such as anandamide, led to intensified efforts to understand the functional significance of endogenous cannabinoids. Manipulation of these endogenous ligands should reveal their functional role, especially as mediated through cannabinoid receptors, and lead to a better understanding of the etiology of cannabis abuse, identification of therapeutic uses of cannabinoids, and establishment of either deleterious or protective effects on the immune system. Studies on the immune system are important since they may allow for articulation of a mechanism by which endogenous cannabinoids modulate immune function. Such modulation may be of consequence among immune compromised individuals, especially AIDS patients. The recent development of selective antagonists for cannabinoid receptor subtypes serve as exciting new probes for fulfilling these objectives. The purpose of this proposal is to continue this multidisciplinary program that will consist of five research projects and an administrative core, to define the functional role of endogenous cannabinoids. Each P.I. is an experienced researcher who will make a unique contribution. Professor Mechoulam proposes to isolate and identify other endogenous substances that modulate the activity of anandamide as well as conduct a synthetic program. Dr. Razdan will continue his synthetic program in which he will provide novel and innovate probes to the other members of the research team. His objectives include preparation of stable and highly potent analogs of the endogenous substances and analogs of SR141716A. Research teams led by Drs. Martin and Pertwee will conduct pharmacological evaluation of endogenous ligands and analogs of endogenous agonists and of the antagonist. These groups also will use both tolerance development and the antagonist to explore the plasticity of the receptor and gene expression. Dr. Martin will address the dependence liability of anandamide. Dr. Kaminski proposes to establish the effects of endogenous ligands on the immune system and to elucidate a natural role of cannabinoids in immune function. Dr. Kaminski has evidence that two endogenous ligands exert different effects on immune cells. The participants have already demonstrated that their collaborative efforts have been most productive and fruitful.