DISPOSITION, METABOLISM & PROCESSING OF OPIATE AGONISTS, ANTAGONISTS & OPIOIDS

性格、新陈代谢

• 批准号: 7954050
• 负责人: MARY J KREEK
• 金额: $ 1.42万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954050
• 关键词: Agonist; Cholecystokinin; Cocaine; Computer Retrieval of Information on Scientific Projects Database; Corticotropin; Corticotropin-Releasing Hormone; Dopamine; Dynorphin A; Dynorphins; Enkephalins; Fluoxetine; Funding; Grant; High Pressure Liquid Chromatography; Hormones; Institution; Mass Spectrum Analysis; Metabolism; Methadone; Methods; Morphine; Narcotic Antagonists; Neuropeptides; Neurotransmitters; Opiates; Opioid Peptide; Oxytocin; Parents; Peptides; Pro-Opiomelanocortin; Process; Proteins; Rattus; Research; Research Personnel; Resources; Source; Substance P; System; Techniques; United States National Institutes of Health; Vasopressins; alcohol effect; beta-Endorphin; drug of abuse; endogenous opioids; extracellular; gamma-MSH; macromolecule; nalmefene; novel; prodynorphin; proenkephalin; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims are A. To develop novel methods using mass spectrometry to qualitatively (and subsequently, semi-quantitatively or quantitatively) determine the presence of multiple neuropeptides derived from a single gene product (e.g. prodynorphin and processed dynorphin A peptides; proenkephalin and processed enkephalin peptides; proopiomelanocortin (POMC) parent peptide and multiple peptides derived from POMC, adrenocorticotropin hormone (ACTH), beta-endorphin, of gamma-melanocyte-stimulating hormone (MSH). B.To use these novel techniques (alone or in combination with HPLC and/or RIA) for the simultaneous qualitative and/or quantitative analysis of opioid peptides and other neuropeptides related to the endogenous opioid system (e.g. Corticotropin releasing factor (CRF), cholecystokinin (CCK), substance P and their processed peptides). C. To use these techniques in studies of the effects of alterations in levels of activity of neurotransmitters on the processing of endogenous opioids (e.g. the effects of altered levels of dopamine on dynorphin processing). D. To use these techniques to study the effects of drugs of abuse and potential treatment agents on opioid peptide processing and degradation (e.g. cocaine, morphine and ethanol effects; methadone, nalmefene and fluoxetine effects). We are currently developing novel MS tools for determining specific endogenous extracellular neuropeptides (including vasopressin and oxytocin) in rat

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 具体目标是 A. 开发使用质谱法定性（随后半定量或定量）确定源自单个基因产物的多种神经肽（例如强啡肽原和加工的强啡肽 A 肽；脑啡肽原和加工的脑啡肽；阿片黑皮质素原 (POMC) 亲本肽和多种神经肽）的新方法。 源自 POMC、促肾上腺皮质激素 (ACTH)、β-内啡肽、γ-黑素细胞刺激激素 (MSH) 的肽。 B. 使用这些新技术（单独或与 HPLC 和/或 RIA 组合）对阿片肽和与内源性相关的其他神经肽进行同步定性和/或定量分析 阿片类系统（例如促肾上腺皮质激素释放因子（CRF）、胆囊收缩素（CCK）、P物质及其加工肽）。 C. 使用这些技术来研究神经递质活性水平的改变对内源性阿片类药物加工的影响（例如多巴胺水平改变对强啡肽加工的影响）。 D. 使用这些 研究滥用药物和潜在治疗药物对阿片肽加工和降解影响的技术（例如可卡因、吗啡和乙醇的影响；美沙酮、纳美芬和氟西汀的影响）。 我们目前正在开发新型 MS 工具，用于测定大鼠中特定的内源性细胞外神经肽（包括加压素和催产素）