Tomohiko Sekioka1, Michiaki Kadode1, Masanori Fujii2, Kazuhito Kawabata3, Takashi Abe4, Michiaki Horiba4, Shigekatsu Kohno2, Takeshi Nabe5. 1. Discovery Research Laboratories II, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan; Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan. 2. Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan. 3. Discovery Research Laboratories II, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan. 4. Department of Pneumology, Ogaki Municipal Hospital, Gifu, Japan. 5. 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.
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.
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: Lora G Bankova; Juying Lai; Eri Yoshimoto; Joshua A Boyce; K Frank Austen; Yoshihide Kanaoka; Nora A Barrett Journal: Proc Natl Acad Sci U S A Date: 2016-05-16 Impact factor: 11.205
Authors: José A Cornejo-García; James R Perkins; Raquel Jurado-Escobar; Elena García-Martín; José A Agúndez; Enrique Viguera; Natalia Pérez-Sánchez; Natalia Blanca-López Journal: Front Pharmacol Date: 2016-09-21 Impact factor: 5.810