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）。 最近 描述这项工作的论文如下：J. Yu，E.R.巴特勒曼， J.H.伍兹，B.T. Chait，M. J. Kreek“强啡肽A（1-8）类似物，E-2078， 在人和恒河猴血液中是稳定的”J. Pharm. Experimental Therapeutics 280（1997）1147-1151. J. Yu，急诊室Butleman，J.H.伍兹， B.T. Chait，M. J. Kreek“强啡肽A（1-8）类似物，E2078， 恒河猴的血脑屏障”J. Pharmacol. Exp. Ther. 282 （1997）633-638。

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, of ?-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). Recent papers describing this work are listed below: J. Yu, E.R. Butleman, 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. J. Yu, E.R. Butleman, J.H. Woods, B.T. Chait, M.J. Kreek "Dynorphin A(1-8) analog, E2078, crosses the blood-brain barrier in rhesus monkeys" J. Pharmacol. Exp. Ther. 282 (1997) 633-638.