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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 其具体目的是：a.开发使用质谱学的新方法来定性(并随后半定量或定量)来自单个基因产品的多个神经肽的存在(例如，前强啡肽和加工的强啡肽A肽；前脑啡肽和加工的脑啡肽；前阿片黑素皮质素(POMC)母体多肽和来自POMC的多个多肽、促肾上腺皮质激素(ACTH)、β-内啡肽、γ-黑素细胞刺激素(MSH)。B.使用这些新技术(单独或结合高效液相色谱和/或放射免疫分析)同时定性和/或定量分析阿片肽和其他与内源性阿片系统相关的神经肽(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.将这些技术用于研究神经递质活性水平的变化对内源性阿片类药物加工的影响(例如，多巴胺水平变化对强啡肽加工的影响)。D.利用这些技术研究滥用药物和潜在的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)。 我们目前正在开发新的MS工具来确定特定的内源性细胞外神经肽。

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.