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Investigation of the metabolic biotransformation of substance P in liver microsomes by liquid chromatography quadrupole ion trap mass spectrometry

Authors

  • Floriane Pailleux,

    1. Groupe de Recherche en Pharmacologie Animal du Québec (GREPAQ), Département de biomedicine vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada
    2. UMR 5280 CNRS Université de Lyon 1, Institut des Sciences Analytiques, Université de Lyon, Villeurbanne cedex, France
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  • Jérôme Lemoine,

    1. UMR 5280 CNRS Université de Lyon 1, Institut des Sciences Analytiques, Université de Lyon, Villeurbanne cedex, France
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  • Francis Beaudry

    Corresponding author
    • Groupe de Recherche en Pharmacologie Animal du Québec (GREPAQ), Département de biomedicine vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada
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F. Beaudry, Groupe de Recherche en Pharmacologie Animal du Québec (GREPAQ), Département de biomédicine vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada. E-mail: francis.beaudry@umontreal.ca

ABSTRACT

Substance P (SP) belongs to the tachykinin family and plays an essential role in pain transmission and in neurogenic inflammation. It can be detected in the central and peripheral nervous systems. The objectives of this study were to establish SP metabolic stability in liver microsomes in three species (rat, mouse and human), and identify and characterize SP metabolites by LC-MS/MS. Endogenous peptide metabolism is not well documented and this is particularly true for neuropeptides participating in neurogenic inflammation. In vitro, T1/2 results in pooled liver microsomes were 9.2, 5.6 and 18.6 min for rat, mouse and human liver microsomes, respectively. Five major SP metabolites were identified and quantified, including C-terminal SP fragments SP3–11, SP5–11, SP6–11, SP8–11 as well as N-terminal fragment SP1–7. The results suggest significant differences between species in SP metabolite concentrations. Consequently, the metabolic profile of each species is distinctive and may have a significant impact on biomolecular mechanisms involved in specific pathophysiological changes. Copyright © 2012 John Wiley & Sons, Ltd.

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