ENDOGENOUS CANNABINOIDS AND BRAIN/IMMUNE FUNCTION

有令人信服的证据表明，内源性大麻素存在于两者中。 大脑和免疫系统。两种G蛋白大麻素受体 被克隆了一种是在整个大脑中发现高浓度， 以及在几个周边组织，而另一个是局部的 只在外围。的分离鉴定 内源性大麻素，如大麻素，导致加强努力， 了解内源性大麻素的功能意义。 这些内源性配体的操作应揭示其功能 作用，特别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， 大麻素的治疗用途，以及建立有害的 或对免疫系统的保护作用。免疫系统研究 是重要的，因为它们可以允许通过 内源性大麻素调节免疫功能。这种调制 在免疫受损的个体中，尤其是 艾滋病患者。选择性拮抗剂的研究进展 大麻素受体亚型作为令人兴奋的新探针， 这些目标。本提案的目的是继续这一 多学科计划，将包括五个研究项目， 一个行政核心，界定内生的职能作用 大麻素每个私家侦探是一位经验丰富的研究人员， 独特的贡献。Mechoulam教授建议分离并鉴定 调节大麻素活性的其他内源性物质， 进行一个综合项目。拉兹丹博士将继续他的 他将提供新颖和创新探测， 研究团队的其他成员。他的目标包括准备 内源性物质的稳定和高效类似物， SR141716A的类似物。由马丁和佩特维博士领导的研究小组将 进行内源性配体和类似物的药理学评价 内源性激动剂和拮抗剂。这些团体也将使用这两个 耐受性的发展和拮抗剂，以探讨可塑性的 受体和基因表达。马丁医生会解决 anandamide的责任卡明斯基博士建议建立的影响， 内源性配体对免疫系统的作用，并阐明 大麻素在免疫功能中的作用卡明斯基博士有证据表明 内源性配体对免疫细胞发挥不同的作用。的 与会者已经证明，他们的合作努力， 是最富有成效和成果的。

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.