title: Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R).
abstract: OBJECTIVE
  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 microg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hutter
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wick
authors.forename: Amy Lightner
authors.initials: AL
authors.lastname: Day
authors.forename: John
authors.initials: J
authors.lastname: Maa
authors.forename: Elena C
authors.initials: EC
authors.lastname: Zerega
authors.forename: Alec C
authors.initials: AC
authors.lastname: Richmond
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Jordan
authors.forename: Eileen F
authors.initials: EF
authors.lastname: Grady
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Mulvihill
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Bunnett
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Kirkwood
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002108:Ceruletide; D004396:Coloring Agents / Q000493:pharmacokinetics; D005070:Evans Blue / Q000493:pharmacokinetics; D008297:Male; D009443:Neuritis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D010179:Pancreas / Q000276:immunology / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D004396:Coloring Agents; D018040:Receptors, Neurokinin-1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D005070:Evans Blue; D002108:Ceruletide; C071423:capsazepine; D002211:Capsaicin