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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 具体目标是A.开发使用质谱法进行定性的新方法（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）。 我们目前正在开发新的质谱工具，用于测定大鼠体内特异性内源性细胞外神经肽（包括加压素和催产素）

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