The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B.
Eosinophilic bronchitis without asthma can cause a persistent non-productive cough which is resistant to bronchodilator therapy. To understand the mechanism of the cough in this disorder, an animal model of eosinophilic bronchitis was developed. Guinea-pigs were treated with transnasal administration of polymyxin B or saline twice a week for 3 weeks. The number of eosinophils in bronchoalveolar lavage fluid increased in polymyxin B-treated animals when compared with those treated with saline. In addition, histological examination showed that the number of eosinophils infiltrated into the tracheal epithelium increased; injury to the tracheal epithelium was greater in polymyxin B-treated animals. The numbers of coughs induced by saline and each concentration of capsaicin (10(-18), 10(-16), 10(-14) M) were greater in the polymyxin B-treated animals. FK-224 (a neurokinin receptor antagonist) decreased the heightened cough reflex in this animal model of eosinophilic bronchitis. These findings suggest that neuropeptides, and particularly neurokinins, are involved in the heightened cough receptor sensitivity in eosinophilic bronchitis without asthma. This has implications for better understanding of this disorder and its treatment.
Ogawa
H
H
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Fujimura
M
M
Saito
M
M
Matsuda
T
T
Akao
N
N
Kondo
K
K
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D004802:Eosinophilia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011112:Polymyxin B; D015320:Tachykinins / Q000037:antagonists & inhibitors
D010456:Peptides, Cyclic; D015320:Tachykinins; C075570:FK 224; D015288:Neurokinin A; D011112:Polymyxin B; D002211:Capsaicin