Effects of a Cysteinyl Leukotriene Dual 1/2 Receptor Antagonist on Antigen-Induced Airway Hypersensitivity and Airway Inflammation in a Guinea Pig Asthma Model

Vol. 155, Suppl. 1, 2011

Article (Fulltext) Article (PDF 1706 KB)

Eosinophils in Allergy and Related Diseases.
Editor(s): Fukuda T. (Tochigi), Ohta K. (Tokyo), Iwamoto I. (Chiba), Fujisawa T. (Mie), Mori A. (Kanagawa), Chihara J. (Akita), Nagata M. (Saitama), Ohno I. (Miyagi), Kato M. (Gunma)

Original Paper

Effects of a Cysteinyl Leukotriene Dual 1/2 Receptor Antagonist on Antigen-Induced Airway Hypersensitivity and Airway Inflammation in a Guinea Pig Asthma Model
Masato Muraki^a, Shu Imbe^b, Hiroshi Santo^b, Ryuji Sato^b, Hiroyuki Sano^b, Takashi Iwanaga^b, Yuji Tohda^b

^aDepartment of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, and
^bDepartment of Respiratory Medicine and Allergology, Kinki University School of Medicine, Osakasayama, Japan

Address of Corresponding Author

Int Arch Allergy Immunol 2011;155 (Suppl. 1):90-95 (DOI: 10.1159/000327439)

Key Words

Asthma
Cysteinyl leukotriene 2 receptor
Airway inflammation
Airway hypersensitivity
BAY-u9773
Montelukast

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. Conclusion: Signaling may contribute to the pathophysiology of asthma via the cysLT1/2 receptor.

Author Contacts

Correspondence to: Dr. Masato Muraki
Department of Respiratory Medicine and Allergology
Nara Hospital, Kinki University Faculty of Medicine
1248-1 Otoda-cho, Ikoma, Nara, 630-0293 (Japan)
Tel. +81 743 77 0880, E-Mail muraki@nara.med.kindai.ac.jp

Article Information

Published online: June 1, 2011
Number of Print Pages : 6
Number of Figures : 4, Number of Tables : 0, Number of References : 27

Cited in Web of Science®

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