Investigation of the metabolism of Substance-P at the blood-brain barrier using LC-MS/MS
Issue Date
2007Author
Chappa, Arvind K.
Cooper, Joshua D.
Audus, Kenneth L.
Lunte, Susan M.
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Metadata
Show full item recordAbstract
Substance P (SP) has been associated with pain, 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 these studies, 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 μM, with approximately 70% of the peptide remaining intact after 5 hrs. The major metabolites of SP were identified by MS to be 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 overtime was obtained. The results from the present study provide us a better understanding of the role of blood-brain barrier in the pharmacology of SP.
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Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.
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Citation
Chappa, A.K., Cooper, J.D., Audus, K.L., and Lunte, S.M. (2007) Investigation of the metabolism of Substance-P at the blood-brain barrier using LC-MS/MS. J. Pharm. Biomed. Anal.43, 1409-1415. PMID: 17118606 http://dx.doi.org/10.1016/j.jpba.2006.10.005
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