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: Tomohiko Sekioka, Michiaki Kadode, Masanori Fujii, Kazuhito Kawabata, Takashi Abe, Michiaki Horiba, Shigekatsu Kohno, Takeshi Nabe
• Journal: Allergology international : official journal of the Japanese Society of Allergology (Allergol Int) Vol. 64 Issue 4 Pg. 351-8 (Oct 2015) ISSN: 1440-1592 [Electronic] England
• PMID: 26433531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Antigens
• Leukotriene Antagonists
• Receptors, Leukotriene
• Leukotriene D4
• cysteinyl leukotriene receptor 2
• leukotriene D4 receptor
• Calcium

Topics

• Aged
• Antigens (immunology)
• Asthma (diagnosis, genetics, metabolism)
• Bronchoconstriction (genetics, immunology)
• Calcium (metabolism)
• Female
• Gene Expression
• Humans
• Immunohistochemistry
• Leukocyte Count
• Leukotriene Antagonists (pharmacology)
• Leukotriene D4 (metabolism)
• Lung (immunology, metabolism, pathology, physiopathology)
• Male
• Middle Aged
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects, metabolism)
• Receptors, Leukotriene (genetics, metabolism)
• Respiratory Function Tests