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Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
The aim of this study was to elucidate the
role of thromboxane A2 (TxA2) 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 TxA2 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 TxB2 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 TxA2 derived from mucous cells potentiated
cough responses to capsaicin in allergic airway inflammation.
allergic airway inflammation; capsaicin; guinea pigs; mRNA; airway lavage fluid
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