Involvement of thromboxane A(2) in airway mucous cells in asthma-related cough.
The aim of this study was to elucidate the role of thromboxane A(2) (TxA(2)) on asthma-related cough in guinea pigs. Animals were immunosensitized and repeatedly challenged with ovalbumin as an antigen. Coughs were induced by the inhalation of 10(-5) M capsaicin solution for 10 min. Thromboxane synthetase (TxS) inhibitor OKY-046 and thromboxane-receptor antagonist AA-2414 significantly inhibited cough responses in repeatedly challenged animals. Inhalation of TxA(2) mimic STA-2- potentiated cough responses in normal and immunosensitized animals but not in repeatedly challenged ones. Moreover, STA-2-potentiated coughs were inhibited by administration of neurokinin-receptor antagonist FK-224. In repeatedly challenged animals, concentration of TxB(2) in airway lavage fluid, expression of TxS mRNA in tracheal epithelia, and the immunostaining intensity against TxS in mucous cells of the epithelium significantly increased compared with normal and sensitized animals. These results suggest that TxA(2) derived from mucous cells potentiated cough responses to capsaicin in allergic airway inflammation.
Xiang
Anbo
A
Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Uchida
Yoshiyuki
Y
Nomura
Akihiro
A
Iijima
Hiroaki
H
Sakamoto
Tohru
T
Ishii
Yukio
Y
Morishima
Yuko
Y
Masuyama
Kuniko
K
Zhang
Minjie
M
Hirano
Kuniyoshi
K
Sekizawa
Kiyohisa
K
D000818:Animals; D001249:Asthma / Q000150:complications*; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003371:Cough / Q000209:etiology* / Q000503:physiopathology*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000473:pathology / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000201:enzymology
D018076:DNA, Complementary; D012333:RNA, Messenger; D013928:Thromboxane A2; C037866:STA 2; D013930:Thromboxane-A Synthase