title: Effects of a cysteinyl leukotriene dual 1/2 receptor antagonist on antigen-induced airway hypersensitivity and airway inflammation in a guinea pig asthma model.
abstract: BACKGROUND
  Little is known about the role of the cysteinyl leukotriene (cysLT) 2 receptor in the pathophysiology of asthma. The aim of this study is to investigate the effects of a cysLT1 receptor antagonist (montelukast) and a dual cysLT1/2 receptor antagonist (BAY-u9773) on airway hypersensitivity and airway inflammation induced by antigen challenge in ovalbumin (OVA)-sensitized guinea pigs.
  
  
  METHODS
  Male Hartley guinea pigs sensitized with OVA were intraperitoneally administered 0.1, 1, or 10 mg/kg of montelukast or 0.1 mg/kg of BAY-u9773 and then challenged with inhaled OVA. Airway reactivity to acetylcholine, inflammatory cells in bronchoalveolar lavage (BAL) fluid, and eosinophil infiltration in airway walls after OVA challenge were evaluated.
  
  
  RESULTS
  Pretreatment with 1 or 10 mg/kg, but not 0.1 mg/kg, of montelukast significantly suppressed airway hypersensitivity and eosinophil infiltration into the BAL fluid. Moreover, 0.1 mg/kg of BAY-u9773 significantly suppressed the development of these markers. The suppressive effects of BAY-u9773, although not significantly different, trended toward being greater than those of montelukast. Although all of the doses of montelukast tested and 0.1 mg/kg of BAY-u9773 significantly suppressed eosinophil infiltration in airway walls, the suppressive effect of BAY-u9773 was significantly greater than that of 0.1 mg/kg of montelukast.
  
  
  CONCLUSIONS
  Signaling may contribute to the pathophysiology of asthma via the cysLT1/2 receptor.
authors.affiliation: Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan. muraki@nara.med.kindai.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Muraki
authors.forename: Shu
authors.initials: S
authors.lastname: Imbe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Santo
authors.forename: Ryuji
authors.initials: R
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sano
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tohda
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003521:Cyclopropanes; D004804:Eosinophils / Q000473:pathology; D006168:Guinea Pigs; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013440:Sulfides
chemical_list: D000085:Acetates; C071435:BAY u9773; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D018077:Receptors, Leukotriene; D013189:SRS-A; D013440:Sulfides; D010047:Ovalbumin; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C093875:montelukast; D000109:Acetylcholine