OPIOID RECEPTORS ON LYMPHOCYTES AND BRAIN

淋巴细胞和大脑上的阿片受体

• 批准号: 6350466
• 负责人: JEAN M BIDLACK
• 金额: $ 9.57万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6350466
• 关键词: cell type; cocaine; drug abuse chemotherapy; drug screening /evaluation; flow cytometry; fluorescent dye /probe; gene expression; heroin; human herpesvirus 6; lymphocyte; nucleus accumbens; opioid receptor; protein sequence; receptor expression; second messengers

DESCRIPTION: (Applicant's Abstract) This K05 Senior Scientist Award is to support Dr. Jean M. Bidlack's research activities. The specific aim of this award is to provide Dr. Bidlack with some release time from grant writing, teaching and administrative responsibilities to cover her salary. This award will allow her to devote the majority of her time to research and the training of graduate students and postdoctoral fellows. Dr. Bidlack will expand her research in studying the expression and regulation of opioid receptors on immune cells. Also, she will continue her studies on medications development for the treatment of heroin and cocaine abuse. These goals will be accomplished within the framework of two RO1 grants and three subcontracts from NIDA. Training activities will be supported by a NIDA Training Grant (T32DA07232). The first project (DA04355 and DA09676) is focused on determining which cells from the immune system express mu, delta and kappa opioid receptors. Studies over the past two years have demonstrated the ability to localize the kappa opioid receptor on mixed immune cell populations by the use of an indirect immunofluorescent amplification procedure combined with flow cytometry and the use of cell surface markers. New fluorescent probes will be evaluated to determine if they can be used to localize mu and delta receptors on lymphocytes. A new area of research involves determining if a protein expressed by the human herpes virus 6 and a homolog of the opioid receptor, based on amino acid sequence, is in fact a functional opioid receptor. This protein will be expressed in COS-7 cells; binding and second messenger studies will determine if the protein is a new functional opioid receptor. The second project (DA03742, DA01674 and U19DA11007) involves evaluating new compounds for their potential as candidates for the treatment of drug abuse. The working hypothesis for which we have produced experimental support is that compounds which release dopamine from the nucleus accumbens promote drug-seeking behavior and those which prevent release of this transmitter prevent drug-seeking behavior. It is known that kappa agonists and mu antagonists inhibit dopamine release in the nucleus accumbens. In collaboration with chemists and behaviorists, we will continue our biochemical and behavioral characterization of new compounds, particularly kappa agonists and mu antagonists. Collectively, these projects will provide new information on the localization and function of the multiple opioid receptors on immune cells and on HHV-6. Also, they will advance efforts in developing drugs to treat cocaine and heroin abuse.

描述：(申请人摘要) K05高级科学家奖是为了支持让·M·比德拉克博士的研究 活动。该奖项的具体目的是为比德拉克博士提供 从赠款撰写、教学和行政管理中释放一些时间 承担起支付工资的责任。这个奖项将使她能够致力于 她的大部分时间都花在研究和培养研究生上 和博士后研究员。比德拉克博士将在研究中扩大她的研究 免疫细胞上阿片受体的表达和调节。另外， 她将继续研究治疗药物的开发。 海洛因和可卡因滥用。这些目标将在 NIDA提供的两笔RO1赠款和三份分包合同的框架。培训 活动将得到NIDA培训补助金(T32DA07232)的支持。这个 第一个项目(DA04355和DA09676)专注于确定哪些单元 来自免疫系统的Mu、Delta和kappa阿片受体的表达。 过去两年的研究已经证明了本地化的能力 Kappa阿片受体在混合免疫细胞群体中的作用 间接免疫荧光扩增结合Flow 细胞学和细胞表面标志物的使用。新的荧光探针将 进行评估以确定它们是否可用于本地化MU和Delta 淋巴细胞上的受体。一个新的研究领域涉及确定一个 人类疱疹病毒6表达的蛋白质和阿片类药物的同系物 基于氨基酸序列的受体实际上是一种功能性阿片类药物 受体。该蛋白将在COS-7细胞中表达；结合和第二 信使研究将确定这种蛋白质是否是一种新的功能阿片类药物 受体。 第二个项目(DA03742、DA01674和U19DA11007)涉及评估新的 化合物作为治疗药物滥用的候选药物的潜力。 我们为其提供实验支持的工作假说是 从伏隔核释出多巴胺的化合物促进 寻找毒品的行为和那些阻止这种递质释放的行为 防止寻毒行为。已知Kappa激动剂和Mu 拮抗剂抑制伏隔核多巴胺的释放。在……里面 与化学家和行为学家的合作，我们将继续我们的 新化合物的生化和行为表征，特别是 Kappa激动剂和Mu拮抗剂。 总的来说，这些项目将提供有关 多种阿片受体在免疫细胞上的定位和功能 以及HHV-6病毒。此外，他们还将推进治疗药物的开发工作 可卡因和海洛因滥用。