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

性格、新陈代谢

• 批准号: 8361484
• 负责人: MARY J KREEK
• 金额: $ 2.61万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361484
• 关键词: Agonist; Cholecystokinin; Cocaine; Corticotropin; Corticotropin-Releasing Hormone; Dopamine; Dynorphin A; Dynorphins; Enkephalins; Fluoxetine; Funding; Grant; High Pressure Liquid Chromatography; Hormones; Mass Spectrum Analysis; Metabolism; Methadone; Methods; Morphine; Narcotic Antagonists; National Center for Research Resources; Neuropeptides; Neurotransmitters; Opiates; Opioid Peptide; Oxytocin; Parents; Peptides; Principal Investigator; Pro-Opiomelanocortin; Process; Proteins; Rattus; Research; Research Infrastructure; Resources; Source; Staging; Substance P; System; Techniques; United States National Institutes of Health; Vasopressins; alcohol effect; beta-Endorphin; cost; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 have recently developied a novel multi-stage MS tool for determining specific endogenous extracellular neuropeptides (including vasopressin and oxytocin) in rat

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 具体目标是A。开发新的方法，使用质谱定性（并且随后，半定量或定量地）确定来源于单个基因产物的多种神经肽的存在（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;阿黑皮素原（POMC）母体肽和衍生自POMC的多种肽，促肾上腺皮质激素（ACTH），β-内啡肽，伽马黑素细胞刺激激素（MSH）。 B.将这些新技术（单独或与HPLC和/或RIA结合）用于同时定性和/或定量分析阿片肽和与内源性阿片系统相关的其他神经肽（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.使用这些技术研究神经递质活性水平的改变对内源性阿片类物质加工的影响（例如多巴胺水平的改变对强啡肽加工的影响）。 D.使用这些技术研究滥用药物和潜在治疗药物对阿片肽加工和降解的影响（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）。 我们最近开发了一种新的多级质谱技术，用于测定大鼠内源性细胞外神经肽（包括加压素和催产素