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.
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.
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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