Involvement of enhanced neurokinin NK3 receptor expression in the severe asthma guinea pig model.
In this study, we investigated the involvement of neurokinin NK3 receptors in a severe asthma model prepared by administering ovalbumin via inhalation three times to systemically sensitized guinea pigs. [3H]senktide, a neurokinin NK3 receptor ligand, showed significant specific binding to the lungs from the model animals, but not to those from negative control animals. The airway responsiveness to intravenous neurokinin B, a neurokinin NK3 receptor agonist, was increased in the model, indicating an increase in functional NK3 receptors. Furthermore, SB 223956 ((-)-3-methoxy-2-phenyl-N-[(1S)-phenylpropyl]quinoline-4-carboxamide), a selective neurokinin NK3 receptor antagonist, significantly inhibited the ovalbumin-induced airway hyperresponsiveness to inhaled methacholine, but it did not show significant effects on the ovalbumin-induced airway narrowing and eosinophil accumulation. These results suggest that the expressed neurokinin NK3 receptors in the severe asthma model are involved in the development of airway hyperresponsiveness.
Mukaiyama
Osamu
O
R&D Project Management Department, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. mukouy@sankyo.co.jp
Morimoto
Kiyoshi
K
Nosaka
Emi
E
Takahashi
Sakiko
S
Yamashita
Makoto
M
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001549:Benzamides / Q000378:metabolism; D001667:Binding, Competitive; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism; D014316:Tritium
D001549:Benzamides; D016085:Bronchoconstrictor Agents; D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; D016210:Methacholine Chloride; D014316:Tritium; C054724:senktide; D013373:Substance P; C073839:SR 48968; D015287:Neurokinin B; D010047:Ovalbumin