Opioid REceptors on Lymphocytes and Brain

淋巴细胞和大脑上的阿片受体

• 批准号: 7173433
• 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/7173433
• 关键词: Affinity; Agonist; Amino Acid Sequence Homology; Antibodies; Award; Binding; Brain; CD8B1 gene; Cell Cycle; Cell surface; Cells; Cocaine; Cocaine Abuse; Collaborations; Dopamine; Drug abuse; Educational process of instructing; Ensure; Fentanyl; Flow Cytometry; Fluorescein; Fluoresceins; Goals; Grant; Heroin; Heroin Abuse; Herpesviridae; Human; Immune; Interphase Cell; Label; Ligands; Localized; Lymphocyte; Lymphocyte Activation; Mentors; Methods; Morphine Derivatives Including Cocaine; Mus; National Institute of Drug Abuse; Nucleus Accumbens; Opioid; Opioid Receptor; Peritoneal Macrophages; Pharmaceutical Preparations; Phycoerythrin; Population; Postdoctoral Fellow; Procedures; Productivity; Property; Receptor Activation; Receptor Cell; Regulation; Relative (related person); Research; Research Activity; Research Personnel; Research Training; Self Administration; Senior Scientist; Senior Scientist Award; Signal Transduction; Staining and Labeling; Streptavidin; Students; T-Cell Receptor; T-Lymphocyte; Testing; Time; Training; Training Activity; Wages; Work; Writing; chemokine; chemokine receptor; drug seeking behavior; kappa opioid receptors; macrophage; mu opioid receptors; naltrindole; next generation; nonhuman primate; novel; prevent; receptor; receptor expression; research study; therapy development; thymocyte

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 高级科学家奖旨在支持 Jean M. Bidlack 博士的研究活动。该奖项的具体目的是为 Bidlack 博士提供一些从资助写作、教学和行政职责中解放出来的时间来支付她的工资。该奖项将使她能够将大部分时间投入到研究以及研究生和博士后研究员的培训上。培训活动将得到 NIDA 培训补助金 (T32 DA07232) 的支持。 Bidlack 博士将扩大她在研究阿片受体对免疫细胞的表达和调节方面的研究背景和专业知识。此外，她还将研究人类疱疹病毒 -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受体的趋化因子激活。这种趋化因子受体 U51 与 kappa 阿片受体具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。我们提供实验支持的工作假设是，从伏隔核释放多巴胺的化合物促进药物寻求行为，而阻止这种递质释放的化合物则阻止药物寻求行为。已知κ激动剂和μ拮抗剂抑制伏隔核中的多巴胺释放。研究正在进一步定义某些化合物的特性，这些化合物可以产生一些？对 mu 受体具有不同活性的激动剂比其他化合物更能减少非人灵长类动物的可卡因自我给药。我们与化学家和行为学家合作，评估新的阿片类药物作为治疗药物滥用的潜在药物疗法。这三个独立项目的目标将在两项 R01 拨款、一项 R21 拨款和 NIDA 的三份分包合同的框架内实现。总的来说，这些项目将提供有关免疫细胞和人类疱疹病毒-6和-7上多种阿片受体的定位和功能的新信息。此外，他们还将努力开发治疗可卡因和海洛因滥用的药物。请求提出本提案是为了向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并确保她作为高级科学家和研究人员持续保持高水平的生产力是必要的。受训者的导师，他们将成为下一代药物滥用研究人员。

项目成果

Synthesis and pharmacological evaluation of 6,7-indolo/thiazolo-morphinans--further SAR of levorphanol.

6,7-吲哚/噻唑吗啡喃的合成和药理评价——左啡诺的进一步SAR。

• DOI: 10.1021/jm0701674
• 发表时间: 2007
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Zhang,Ao;Li,Fuying;Ding,Chunyong;Yao,Qizhen;Knapp,BrianI;Bidlack,JeanM;Neumeyer,JohnL
• 通讯作者: Neumeyer,JohnL

Synthesis and pharmacology of 8-amino-3-[(tetrahydro-2-furanyl)methyl] benzomorphan.

8-氨基-3-[(四氢-2-呋喃基)甲基]苯并吗喃的合成和药理学。

• 发表时间: 2003
• 期刊: Yao xue xue bao = Acta pharmaceutica Sinica.
• 作者: Zhou,Qun;Duan,Wen-hu;Cohen,DanaJ;Bidlack,JeanM;Wentland,MarkP
• 通讯作者: Wentland,MarkP

Phenobarbital withdrawal seizures may occur over several weeks before remitting: human data and hypothetical mechanism.

• DOI: 10.1016/j.seizure.2008.06.014
• 发表时间: 2009-01
• 期刊: SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
• 影响因子: 3
• 作者: Bidlack, Jean M.;Morris, Harold H., III
• 通讯作者: Morris, Harold H., III

Syntheses and opioid receptor binding affinities of 8-amino-2,6-methano-3-benzazocines.

• DOI: 10.1021/jm020429w
• 发表时间: 2003-02
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: M. Wentland;Y. Ye;C. Cioffi;R. Lou;Qun Zhou;Guoyou Xu;W. Duan;C. Dehnhardt;Xufeng Sun;D. J. Cohen;J. Bidlack

Syntheses and opioid receptor binding properties of carboxamido-substituted opioids.

• DOI: 10.1016/j.bmcl.2008.10.134
• 发表时间: 2009
• 期刊: Bioorganic & medicinal chemistry letters
• 影响因子: 2.7
• 作者: M. Wentland;R. Lou;Qun Lu;Yigong Bu;Melissa A. VanAlstine;D. J. Cohen;J. Bidlack