Two Pharmacological Phases in Antigen-Induced Immediate Airway Response in Rats(Pharmacology)

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概要

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• The pharmacological profiles of antigen-induced immediate airway response (IAR) in rats are not fully understood. In this study, we established an ovalbumin (OVA)-induced IAR model using noninvasive measurement in rats, and evaluated the effects of commonly used and effective antiasthmatic drugs, i.e. ketotifen (antihistamine), pranlukast (anti-leukotriene C_4/D_4/E_4 (LT)), seratrodast (anti-thromboxane A_2 (TXA_2)), salbutamol (β2-agonist), and prednisolone (steroid). The rat IAR model exhibited an optimal rapid airway response, and salbutamol inhalation completely suppressed the IAR. Ketotifen inhibited only the quick phase (QP; the reaction from 3 to 6min after challenge), while pranlukast and seratrodast suppressed only the early phase (EP; the reaction from 6 to 30min after challenge). Prednisolone inhibited both QP and EP. Further, continuous administration of compound 48/80, which depletes connective tissue mast cells (CTMC), partially inhibited QP but not EP. In conclusion, these findings suggest that the pharmacological profiles of noninvasive rat IAR are similar to those of asthmatic patients, and that rat IAR exhibits additional, immunological diverse characteristics, i.e. QP caused by the exocytosis of mediators in CTMCs and EP mediated by LT and TXA_2, which are produced by mucosal mast cells (MMCs) and possibly by other types of cells. This is the first report about the comprehensive pharmacological profiles of rodent IAR model, and these analyses of rat IAR model may help expand our understanding of the diverse mechanisms underlying human asthmatic diseases.

• 2008-12-01

著者

• Miyagawa Naoki

  Central Pharmaceutical Research Institute Japan Tobacco Inc.

• Miyagawa Naoki

  岐阜薬科大学 薬理学

• Miyagawa Naoki

  Department Of Pharmacology Gifu Pharmaceutical University

• Kato Toshinobu

  Central Pharmaceutical Research Institute Japan Tobacco Inc.

• Shibata Tsutomu

  Central Pharmaceutical Research Institute Japan Tobacco Inc.

• Tanaka Masaru

  Central Pharmaceutical Research Institute Japan Tobacco Inc.

• IWASAKI Hidenori

  Central Pharmaceutical Research Institute, Japan Tobacco, Inc.

• WAKITANI Korekiyo

  Central Pharmaceutical Research Institute, Japan Tobacco, Inc.

• Iwasaki Hidenori

  Central Pharmaceutical Research Institute Japan Tobacco Inc.

• Wakitani Korekiyo

  Central Pharmaceutical Research Institute Japan Tobacco Inc.

関連論文

• Two Pharmacological Phases in Antigen-Induced Immediate Airway Response in Rats(Pharmacology)
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• Pharmacological Analysis of Antigen-Induced Late Airway Response in Rats(Pharmacology)

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