title: Expression of CysLT2 receptors in asthma lung, and their possible role in bronchoconstriction.
abstract: BACKGROUND
  The expression and functional role of CysLT2 receptors in asthma have not been clarified. In this study, we evaluated CysLT2 receptors expression, and effects of CysLT2-and CysLT1/2-receptor antagonists on antigen-induced bronchoconstriction using isolated lung tissues from both asthma and non-asthma subjects.
  
  
  METHODS
  CysLT1 and CysLT2 receptors expression in asthma and non-asthma lung tissue preparations was examined in immunohistochemistry experiments, and their functional roles in antigen-induced bronchoconstriction were assessed using ONO-6950, a dual CysLT1/2-receptor antagonist, montelukast, a CysLT1 receptor antagonist, and BayCysLT2RA, a CysLT2 receptor-specific antagonist.
  
  
  RESULTS
  CysLT1 receptors were expressed on the bronchial smooth muscle and epithelium, and on alveolar leukocytes in 5 in 5 non-asthma subjects and 2 in 2 asthma subjects. On the other hand, although degrees of CysLT2 receptors expression were variable among the 5 non-asthma subjects, the expression in the asthma lung was detected on bronchial smooth muscle, epithelium and alveolar leukocytes in 2 in 2 asthma subjects. In the non-asthma specimens, antagonism of CysLT2 receptors did not affect antigen-induced bronchial contractions, even after pretreatment with the CysLT1-receptor specific antagonist, montelukast. However, in the bronchus isolated from one of the 2 asthma subjects, antagonism of CysLT2 receptors suppressed contractions, and dual antagonism of CysLT1 and CysLT2 receptors resulted in additive inhibitory effect on anaphylactic contractions.
  
  
  CONCLUSIONS
  CysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population.
authors.affiliation: Discovery Research Laboratories II, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan; Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sekioka
authors.affiliation: Discovery Research Laboratories II, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan; Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kadode
authors.affiliation: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Discovery Research Laboratories II, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Kawabata
authors.affiliation: Department of Pneumology, Ogaki Municipal Hospital, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Pneumology, Ogaki Municipal Hospital, Gifu, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Horiba
authors.affiliation: Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Shigekatsu
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan; Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: t-nabe@pharm.setsunan.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabe
mesh_terms: D000368:Aged; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D016084:Bronchoconstriction / Q000235:genetics / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests
chemical_list: D000941:Antigens; D020024:Leukotriene Antagonists; D018077:Receptors, Leukotriene; D017998:Leukotriene D4; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; D002118:Calcium
keywords: Airway smooth muscle; Anti-asthma drugs; CysLT receptors; Cysteinyl leukotrienes; Leukotriene receptor antagonist