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

具体目标是：A.为了开发新的方法， 解吸扩展范围质谱定性（和 随后，半定量地或定量地）测定 存在源自单一基因产物的多种神经肽 (e.g.前强啡肽和加工强啡肽A肽 和加工的脑啡肽;阿黑皮素原（POMC）母体 促肾上腺皮质激素，POMC衍生肽和多肽 激素（ACTH），？-内啡肽促黑素细胞激素 然后呢？MSH）。 B。使用这些新技术（单独或组合 使用HPLC和/或RIA）进行同时定性和/或 阿片肽和其他神经肽的定量分析 与内源性阿片样物质系统相关（如促肾上腺皮质激素释放 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， 内源性阿片样物质的加工（例如， 多巴胺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治疗药物对 阿片肽加工和降解（例如可卡因、吗啡和 乙醇效应;美沙酮、纳美芬和氟西汀效应）。 论文 描述这项工作的论文已经发表（见下文）或正在印刷。 J. Yu，B.T. Chait，L.Toll和M. J. Kreek“体外非iceptin 人血液中的生物转化”肽17（1996）873-876。 1.5 J. 余，急诊室放大图片作者：J. Chait，M. J. Kreek“体外 强啡肽A（1-17）在人和恒河猴体内的生物转化相似 基质辅助激光解吸/电离法研究猴血 Mass Spectrometry”J. Pharmacology and Experimental Therapeutics，279 （1996）507 - 514。 J. Z. Chou，B.T. Chait，R.Wang，M.J. Kreek Dynorphin A（1-17）and Dynorphin A“ （1-13）人血液中的肽，离体”。 肽。 （Tarrytown，NY） 17（1996）983-990。 J. Yu，急诊室Butelman，J.H.伍兹，B.T. Chait，M.J. 强啡肽A（1-8）类似物E-2078在人和恒河猴中稳定 Monkey Blood”J. Pharm. Experimental Therapeutics 280（1997） 1147-1151.

The specific aims are: A. To develop novel methods using laser desorption extended-range 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), ?-endorphin, ?-melanocyte-stimulating hormone (MSH) and ?-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). Papers describing this work were published (see below) or are in press. J. Yu, B.T. Chait, L.Toll and M.J. Kreek "Noniceptin in vitro Biotransformation in Human Blood" Peptides 17 (1996) 873-876. 1.5 J. Yu, E.R. Butelman, J.H Woods, B.T. Chait, M. J. Kreek "In vitro Biotransformation of Dynorphin A (1-17) is Similar in Human and Rhesus Monkey Blood as studied by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry" J. Pharmacology and Experimental Therapeutics, 279 (1996) 507 - 514. J. Z. Chou, B.T. Chait, R.Wang, M.J. Kreek "Differential Biotransformation of Dynorphin A (1-17) and Dynorphin A (1-13) Peptides in Human Blood, ex vivo". Peptides. (Tarrytown, NY) 17 (1996) 983-990. J. Yu, E.R. Butelman, J.H. Woods, B.T. Chait, M.J. Kreek "Dynorphin A(1-8) Analog, E-2078, is stable in Human and Rhesus Monkey Blood" J. Pharm. Experimental Therapeutics 280 (1997) 1147-1151.