Participation of thromboxane A2 in the cough response in guinea-pigs: antitussive effect of ozagrel

The purpose of this study was to investigate the involvement of thromboxane A2 (TXA2) in the cough response in a guinea-pig cough model. Here, we describe results obtained using a selective TXA2 synthetase inhibitor, ozagrel, and a selective TXA2 agonist, U-46619. Guinea-pigs were anaesthetized and exposed to an aerosol of capsaicin (100 μM) to elicit coughing. The number of coughs was 20.0±5.8 during capsaicin provocation (5 min), but only 2.8±0.4 during a 5-min inhalation of phosphate-buffered saline (PBS) (P<0.05). TXB2 levels in BAL were 101.4±8.0 and 58.4±8.7 pg ml−1 following capsaicin and PBS inhalation, respectively (P<0.01), but there was no intergroup difference in the cell populations in BAL. Inhalation of U-46619 did not induce a cough response by itself at concentrations of 100 ng ml−1 to 10 μg ml−1. However, it caused a 2 fold increase in the number of capsaicin-induced coughs. To explore the source of the TXA2, BAL cells were stimulated with capsaicin and the supernatants collected for analysis. The TXB2 concentration in BAL was increased dose-dependently, indicating that TXA2 is released from BAL cells in response to capsaicin. Ozagrel was administered orally 1 h before a 5 min capsaicin provocation and the number of coughs was counted during the capsaicin inhalation. Ozagrel decreased the number of coughs dose-dependently (ED50 value, 26.3 mg kg−1). These results show that TXA2 modulates the capsaicin-induced cough response by increasing capsaicin-sensitivity. British Journal of Pharmacology (2000) 131, 266–270; doi:10.1038/sj.bjp.0703553