Opioid REceptors on Lymphocytes and Brain

淋巴细胞和大脑上的阿片受体

• 批准号: 7017098
• 负责人: JEAN M BIDLACK
• 金额: $ 11.93万
• 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 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017098
• 关键词: T lymphocyte; cell cycle; cell type; cellular immunity; cocaine; cytotoxic T lymphocyte; drug abuse chemotherapy; drug screening /evaluation; flow cytometry; fluorescent dye /probe; gene expression; helper T lymphocyte; heroin; human herpesvirus 6; immunofluorescence technique; laboratory mouse; leukocyte activation /transformation; macrophage; nucleus accumbens; opioid receptor; protein sequence; receptor expression; second messengers; suppressor T lymphocyte; tissue /cell culture

DESCRIPTION (provided by applicant): 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. Training activities will be supported by a NIDA Training Grant (T32 DA07232). Dr. Bidlack will expand her research background and expertise in studying the expression and regulation of opioid receptors on immune cells. Also, she will investigate whether a chemokine receptor expressed on human herpes virus -6 and -7 binds opioids, and if opioids alter chemokine activation of the receptor. This chemokine receptor, U51, shares considerable amino acid sequence homology and similarity with the kappa opioid receptor. In addition, ongoing studies directed at medications development for the treatment of heroin and cocaine abuse will continue. 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. Studies are further defining properties of select compounds that make some ? agonists with varying activity at mu receptors better at reducing cocaine self-administration in nonhuman primates than other compounds. In collaboration with chemists and behaviorists, we are evaluated new opioids as potential pharmacotherapeutics for treating drug abuse. The goals of these three independent projects will be accomplished within the framework of two R01 grants, a R21 grant, and three subcontracts from NIDA. Collectively, these projects will provide new information on the localization and function of the multiple opioid receptors on immune cells and on the human herpes viruses -6 and -7. Also, they will advance efforts in developing drugs to treat cocaine and heroin abuse. The present proposal is being requested in order to provide the candidate with stability of support, which is necessary for her continued commitment to research in the field of drug abuse and to ensure her sustained high level of productivity as both a senior scientist, and as a mentor for trainees, who will be the next generation of drug abuse researchers.

描述(由申请人提供)： 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。这一奖项的具体目的是为比德拉克博士提供一些时间，让她从撰写拨款、教学和行政责任中解脱出来，以支付她的工资。这一奖项将使她能够将大部分时间投入到研究和研究生和博士后研究员的培训中。培训活动将得到NIDA培训补助金(T32 DA07232)的支持。比德拉克博士将扩大她在研究免疫细胞上阿片受体的表达和调节方面的研究背景和专业知识。此外，她还将调查人类疱疹病毒-6和-7上表达的趋化因子受体是否与阿片类药物结合，以及阿片类药物是否会改变该受体的趋化因子激活。趋化因子受体U51与kappa阿片受体有相当大的氨基酸序列同源性和相似性。此外，针对治疗海洛因和可卡因滥用的药物开发的正在进行的研究将继续进行。我们已经产生了实验支持的工作假说是，从伏隔核释放多巴胺的化合物促进药物寻找行为，而那些阻止这种递质释放的化合物阻止药物寻找行为。已知Kappa激动剂和Mu拮抗剂抑制伏隔核多巴胺的释放。研究正在进一步定义精选化合物的性质，这些化合物可以制造一些？与其他化合物相比，在u受体上具有不同活性的激动剂在减少非人类灵长类动物的可卡因自我给药方面效果更好。在与化学家和行为学家的合作下，我们被评估为治疗药物滥用的潜在药物疗法的新阿片类药物。这三个独立项目的目标将在NIDA的两笔R01赠款、一笔R21赠款和三份分包合同的框架内实现。总的来说，这些项目将提供关于免疫细胞和人类疱疹病毒-6和-7上多个阿片受体的定位和功能的新信息。此外，他们还将推进治疗可卡因和海洛因滥用的药物开发工作。要求提供本提案是为了为候选人提供稳定的支持，这对于她继续致力于药物滥用领域的研究是必要的，并确保她作为资深科学家和受训人员的导师保持高水平的生产力，这些受训人员将成为下一代药物滥用研究人员。