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

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。子项目和 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. 开发新方法，使用质谱法定性（随后半定量或定量）确定源自单基因产物的多种神经肽的存在（例如强啡肽和加工的强啡肽 A 肽；脑啡肽原和加工的脑啡肽；阿黑皮质素原 (POMC) 母肽和源自 POMC、促肾上腺皮质激素激素的多种肽B. 使用这些新技术（单独或与 HPLC 和/或 RIA 结合）对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）进行同步定性和/或定量分析。 C. 使用这些技术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类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型 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.