title: Proteinase-activated receptor-2 activation evokes oesophageal longitudinal smooth muscle contraction via a capsaicin-sensitive and neurokinin-2 receptor-dependent pathway.
abstract: BACKGROUND
  Intraluminal acid evokes sustained oesophageal longitudinal smooth muscle (LSM) contraction and oesophageal shortening, which may play a role in oesophageal pain and the aetiology of hiatus hernia. In the opossum model, this reflex has been shown to involve mast cell activation and release of neurokinins from capsaicin-sensitive neurons. The aim of this study was to determine whether proteinase-activated receptor-2 (PAR-2) activation evokes reflex LSM contraction via similar mechanisms.
  
  
  METHODS
  Tension recording studies were performed using opossum oesophageal LSM strips in the presence and absence of pharmacological agents. In addition, the effect of trypsin on single isolated LSM cells was determined using videomicroscopy, and the expression of PAR-2 in oesophageal tissue was examined using immunohistochemistry.
  
  
  RESULTS
  The PAR-2 agonist trypsin evoked sustained, concentration-dependent contraction of LSM muscle strips, but had no effect on isolated LSM cells. The trypsin-induced contraction was blocked by capsaicin desensitization, substance P (SP) desensitization or application of the selective neurokinin-2 (NK-2) receptor antagonist MEN 10376. Immunohistochemistry revealed co-localization of SP, calcitonin gene-related peptide and PAR-2 in axons of opossum oesophageal LSM.
  
  
  CONCLUSIONS
  Longitudinal smooth muscle contraction induced by trypsin involves capsaicin-sensitive neurons and subsequent activation of NK-2, which is identical to the pathway involved in acid-induced LSM contraction and oesophageal shortening. This suggests that acid-induced LSM contraction may involve mast cell-derived mediators that activate capsaicin-sensitive neurons via PAR-2.
authors.affiliation: Gastrointestinal Diseases Research Unit, Kingston General Hospital Queens University, Kingston, ON, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: D V
authors.initials: DV
authors.lastname: Miller
authors.forename: S
authors.initials: S
authors.lastname: Lourenssen
authors.forename: R W
authors.initials: RW
authors.lastname: Wells
authors.forename: M G
authors.initials: MG
authors.lastname: Blennerhassett
authors.forename: W G
authors.initials: WG
authors.lastname: Paterson
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D009893:Opossums; D010446:Peptide Fragments / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D044464:Receptor, PAR-2; D018041:Receptors, Neurokinin-2; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D015288:Neurokinin A; D014357:Trypsin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin