title: Substance P is generated in vivo following nasal challenge of allergic individuals with bradykinin.
abstract: BACKGROUND
  Bradykinin, a potent inflammatory mediator, is released during allergic and non-allergic rhinitis and asthma in man. Nasal bradykinin challenge induces a dose-dependent plasma leakage into the nasal cavity and relevant symptoms of rhinitis.
  
  
  OBJECTIVE
  We now report on substance P generation during nasal bradykinin challenge in vivo.
  
  
  METHODS
  The effect of locally applied bradykinin on substance P generation was studied in nine individuals, allergic to grass pollen and six non-allergic controls. In the allergics TAME-esterase activity, histamine and substance P concentrations were measured in nasal lavages and correlated to the clinical symptoms.
  
  
  RESULTS
  Substance P concentrations in nasal lavages increased in a dose-dependent fashion during nasal bradykinin challenge in both groups. In the allergic group Substance P-increases correlated with the production of TAME-esterase activity (r = 0.9, P < 0.05) whereas these allergic individuals did not produce any histamine increases. The generation of substance P and the increase of TAME-esterase activity was associated with the onset of clinical symptoms. Correlation of oedema and hypersecretion to substance P were significant by linear regression analysis (r = 0.88, P < 0.005 and r = 0.89, P < 0.02, respectively). Bradykinin induced irritations like burning and itching were short-term and rare. Serial dilutions of nasal washes produced Substance P-RIA displacement curves that paralleled the standard curve and recovery of standard substance P that was added to nasal washes was 76 +/- 4% (mean +/- SEM), n = 8.
  
  
  CONCLUSIONS
  Bradykinin induces in vivo a dose-dependent plasma leakage into the nasal cavity without affecting mast cells, but stimulates nerve endings resulting in the release of the neuropeptide substance P.
authors.affiliation: Universitätsklinikum Rudolf Virchow, Clinical Immunology and Asthma OPD, Freie Universität Berlin, Germany.
authors.forename: C R
authors.initials: CR
authors.lastname: Baumgarten
authors.forename: A
authors.initials: A
authors.lastname: O'Connor
authors.forename: D
authors.initials: D
authors.lastname: Dokic
authors.forename: K D
authors.initials: KD
authors.lastname: Schultz
authors.forename: G
authors.initials: G
authors.lastname: Kunkel
mesh_terms: D000293:Adolescent; D000328:Adult; D001920:Bradykinin; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D009299:Nasal Provocation Tests; D010447:Peptide Hydrolases / Q000032:analysis; D013373:Substance P / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D013373:Substance P; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D001920:Bradykinin