Thromboxane A2 mediates cation-induced airway hyperresponsiveness through the bradykinin B2 receptor in guinea pigs

• Main Authors: Tomohiko Shirotani, Hitoshi Maeda, Yoshihiro Nishimura, Mitsuhiro Yokoyama
• Format: Article
• Language: English
• Published: Elsevier 1999-01-01
• Series: Allergology International
• Subjects: airway hyperresponsiveness; bradykinin; cationic protein; low molecular weight heparin; poly- L-lysine; 6-keto-PGF1α; thromboxane A2
• Online Access: http://www.sciencedirect.com/science/article/pii/S1323893015314696
• ISSN: 1323-8930

To elucidate the mechanisms of cationic protein-induced airway hyperresponsiveness (AHR), the airway response to methacholine, and the concentrations of thromboxane B2 (TXB2) and 6-keto-PGF1α in the bronchoalveolar lavage fluid (BALF) of guinea-pigs were measured after inhalation of poly-L-lysine (P-L-L). The airway responsiveness (AR) was evaluated by specific airway resistance. The inhalation of P-L-L significantly enhanced AR to methacholine, and increased TXB2 and 6-keto-PGF1α in the BALF. The enhanced AR and the increase of TXB2 and 6-keto-PGF1α were both significantly inhibited by pretreatment with low molecular weight heparin (LMWH; anionic protein; 10 mg/mL for 6 min inhalation). Furthermore, thromboxane (TX) synthase inhibitor (ozagrel), thromboxane A2 (TXA2) receptor antagonist (ONO-3708), and bradykinin B2 receptor antagonist (BBRA; Nα-adamantaneacetyl-D-Arg [Hyp3, Thi5,8, D-Phe7]-bradykinin) inhibited the cation-induced AHR. BBRA significantly inhibited the increase of those mediators in the BALF. The data suggest that TXA2, which is newly generated by the stimulation of the bradykinin B2 receptor after inhalation of cationic proteins, plays an important role in cationic protein-induced AHR in guinea pigs.