Investigation of the metabolism of substance P at the blood-brain barrier using LC-MS/MS
Investigation of the metabolism of substance P at the blood-brain barrier using LC-MS/MS
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DOI：
10.1016/j.jpba.2006.10.005
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发表时间：
2007-03-12
影响因子：
3.4
通讯作者：
Lunte, Susan M.
中科院分区：
文献类型：
--
作者：
Chappa, Arvind K.;Cooper, Joshua D.;Lunte, Susan M.
P物质（SP）与疼痛和抑郁以及神经退行性疾病有关。许多这些不同的行动SP可以潜在地归因于SP代谢物产生的血脑屏障（BBB）。在这项研究中，使用BBB和LC-MS/MS的体外模型研究了SP的代谢。发现P物质代谢在100 nM至10 μ M的浓度范围内是不饱和的。5小时后约70%的肽保持完整。SP的主要代谢产物经MS鉴定为3-11和5-11。在我们的研究中还发现了两种以前未报道的代谢物5-11和6-11。还鉴别了其他几种次要SP代谢产物，包括1-9和2-11。获得了随时间推移由BBB产生的SP代谢物的谱。本研究的结果提供了对血脑屏障在SP药理学中作用的更好理解。（c）2006 Elsevier B. V.保留所有权利。
Substance P (SP) has been associated with pain and depression as well as neurodegenerative diseases. Many of these diverse actions of SP can potentially be attributed to SP metabolites generated at the blood-brain barrier (BBB). In this study, the metabolism of SP was investigated using an in vitro model of the BBB and LC-MS/MS. Substance P metabolism was found to be non-saturable in the concentration range of 100 nM to 10 mu M. with approximately 70% of the peptide remaining intact after 5 h. The major metabolites of SP were identified by MS as 3-11 and 5-11. Two previously unreported metabolites, 5-11 and 6-11, were also found in our studies. Several additional minor SP metabolites, including 1-9 and 2-11, were also identified. A profile of the SP metabolites generated by the BBB over time was obtained. The results from the present study provide a better understanding of the role of the blood-brain barrier in the pharmacology of SP. (c) 2006 Elsevier B.V. All rights reserved.