Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis

Jaimie D. Nathan, Akash A. Patel, Douglas C. McVey, Jean E. Thomas, Veronica Prpic, Steven R. Vigna, Rodger A. Liddle

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

We examined whether the capsaicin vanilloid receptor-1 (VR1) mediates substance P (SP) release from primary sensory neurons in experimental pancreatitis. Pancreatitis was achieved by 12 hourly injections of caerulein (50 μg/kg ip) in mice. One group received capsazepine (100 μmol/kg sc), a competitive VR1 antagonist, at 4-h intervals. Neurokinin-1 receptor (NK1R) internalization in acinar cells, used as an index of endogenous SP release, was assessed by immunocytochemical quantification of NK1R endocytosis. The severity of pancreatitis was assessed by measurements of serum amylase, pancreatic myeloperoxidase (MPO) activity, and histological grading. Caerulein administration caused significant elevations in serum amylase and pancreatic MPO activity, produced histological evidence of pancreatitis, and caused a dramatic increase in NK1R endocytosis. Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis. These results demonstrate that repeated caerulein stimulation causes experimental pancreatitis that is mediated in part by stimulation of VR1 on primary sensory neurons, resulting in endogenous SP release.

Original languageEnglish (US)
Pages (from-to)G1322-G1328
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number5 44-5
StatePublished - Dec 18 2001

Keywords

  • Capsazepine
  • Neurogenic inflammation
  • Neurokinin-1 receptor
  • Pancreatic acinar cells
  • Primary sensory neurons

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Nathan, J. D., Patel, A. A., McVey, D. C., Thomas, J. E., Prpic, V., Vigna, S. R., & Liddle, R. A. (2001). Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 281(5 44-5), G1322-G1328.