Two pharmacological phases in antigen-induced immediate airway response in rats.
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 (beta2-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 6 min after challenge), while pranlukast and seratrodast suppressed only the early phase (EP; the reaction from 6 to 30 min 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.
Miyagawa
Naoki
N
Central Pharmaceutical Research Institute, Japan Tobacco, Inc., Takatsuki, Osaka 569-1125, Japan. naoki.miyagawa@ims.jti.co.jp
Iwasaki
Hidenori
H
Kato
Toshinobu
T
Tanaka
Masaru
M
Shibata
Tsutomu
T
Wakitani
Korekiyo
K
D000280:Administration, Inhalation; D058647:Adrenergic alpha-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology*; D007665:Ketotifen / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D016227:Benzoquinones; D002867:Chromones; D006538:Heptanoic Acids; D006635:Histamine H2 Antagonists; D020024:Leukotriene Antagonists; D003189:p-Methoxy-N-methylphenethylamine; C060230:seratrodast; D013928:Thromboxane A2; D010047:Ovalbumin; D011239:Prednisolone; D000420:Albuterol; C047681:pranlukast; D007665:Ketotifen