Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R)

Matthew M. Hutter, Elizabeth C. Wick, Amy Lightner Day, John Maa, Elena C. Zerega, Alec C. Richmond, Thomas H. Jordan, Eileen F. Grady, Sean J. Mulvihill, Nigel W. Bunnett, Kimberly S. Kirkwood

Research output: Contribution to journalArticle

Abstract

Objectives: The transient receptor potential vanilloid 1 (TRPV-1) is an ion channel found on primary sensory afferent neurons. Activation of TRPV-1 leads to the release of the proinflammatory neuropeptide substance P (SP). SP then binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and promotes extravasation of plasma and proteins into the interstitial tissue and neutrophil infiltration, a process called neurogenic inflammation. We tested 2 hypotheses: (1) activation of TRPV-1 in the pancreas leads to interstitial edema and neutrophil infiltration and (2) TRPV-1-induced plasma extravasation is mediated by the release of SP and activation of the NK1-R in the rat. Methods: We measured extravasation of the intravascular tracer Evans blue as an index of plasma extravasation and quantified pancreas tissue myeloperoxidase activity (MPO) as a marker of neutrophil infiltration. The severity of inflammation following intravenous infusion of the secretagogue cerulein (10 μ/kg/h x 4 hours) was assessed using a histologic scoring system. Results: Intravenous injection of the TRPV-1 agonist capsaicin induced a dose-dependent increase in Evans blue accumulation in the rat pancreas (P < 0.05 vs. vehicle control). This effect was blocked by pretreatment with the TRPV-1 antagonist capsazepine (1.8 mg/kg), or the NK1-R antagonist CP 96,345 (1 mg/kg). Capsazepine also reduced cerulein-induced Evans blue, MPO, and histologic severity of inflammation in the pancreas but had no effect on serum amylase. Conclusion: Activation of TRPV-1 induces SP-mediated plasma extravasation in the rat pancreas via activation of the NK1-R. TRPV-1 mediates neurogenic inflammation in cerulein-induced pancreatitis in the rat.

Original languageEnglish (US)
Pages (from-to)260-265
Number of pages6
JournalPancreas
Volume30
Issue number3
DOIs
StatePublished - Apr 2005

Keywords

  • Capsaicin
  • Capsaicin receptor
  • Capsazepine
  • Evans blue
  • Pancreatitis
  • Rats
  • Substance P

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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    Hutter, M. M., Wick, E. C., Day, A. L., Maa, J., Zerega, E. C., Richmond, A. C., Jordan, T. H., Grady, E. F., Mulvihill, S. J., Bunnett, N. W., & Kirkwood, K. S. (2005). Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R). Pancreas, 30(3), 260-265. https://doi.org/10.1097/01.mpa.0000153616.63384.24