OPIOID RECEPTORS ON LYMPHOCYTES AND BRAIN

淋巴细胞和大脑上的阿片受体

• 批准号: 6028177
• 负责人: JEAN M BIDLACK
• 金额: $ 9.29万
• 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/6028177
• 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） K 05高级科学家奖旨在支持Jean M. Bidlack的研究 活动 该奖项的具体目的是为比德莱克博士提供 从拨款写作、教学和行政管理中获得一些空闲时间 她的责任是支付工资。 这个奖项将使她能够 她的大部分时间用于研究和培养研究生 和博士后研究员。 比德莱克博士将扩大她的研究， 免疫细胞上阿片受体的表达和调节。 还有， 她将继续她的研究药物开发的治疗 海洛因和可卡因滥用 这些目标将在 该项目由NIDA的两项RO 1赠款和三项分包合同组成。 培训 活动将得到NIDA培训补助金（T32 DA 07232）的支持。 的 第一个项目（DA 04355和DA 09676）的重点是确定哪些细胞 表达μ、δ和κ阿片受体。 过去两年的研究表明， 混合免疫细胞群上的κ阿片受体， 间接免疫荧光扩增结合流式细胞术 流式细胞术和细胞表面标记的使用。 新的荧光探针将 以确定它们是否可用于定位μ和δ 淋巴细胞上的受体。 一个新的研究领域涉及确定一个 由人类疱疹病毒6和阿片样物质的同系物表达的蛋白质 基于氨基酸序列的受体实际上是一种功能性阿片样物质 受体的 该蛋白将在COS-7细胞中表达;结合和第二次表达。 信使研究将确定这种蛋白质是否是一种新的功能性阿片样物质 受体的 第二个项目（DA 03742、DA 01674和U19 DA 11007）涉及评估新的 化合物作为治疗药物滥用的候选物的潜力。 我们已经得到实验支持的工作假设是： 从脑桥核释放多巴胺的化合物 寻求药物的行为和那些阻止释放这种发射器 防止吸毒行为。 已知kappa激动剂和mu 拮抗剂抑制丘脑核中的多巴胺释放。 在 与化学家和行为学家合作，我们将继续我们的 新化合物的生物化学和行为表征，特别是 κ激动剂和μ拮抗剂。 总的来说，这些项目将提供关于 免疫细胞上多种阿片受体的定位和功能 以及HHV-6病毒 此外，他们还将努力开发药物， 可卡因和海洛因滥用