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

Autor: Tomohiko Shirotani, Hitoshi Maeda, Yoshihiro Nishimura, Mitsuhiro Yokoyama
Jazyk: angličtina
Rok vydání: 1999
Předmět:
Zdroj: Allergology International, Vol 48, Iss 1, Pp 61-68 (1999)
Druh dokumentu: article
ISSN: 1323-8930
1440-1592
DOI: 10.1046/j.1440-1592.1999.00118.x
Popis: 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.
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