Nambu F, Motoishi M, Omawari N, Okegawa T, Kawasaki A, Ikeda S
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Jpn J Pharmacol. 1990 Feb;52(2):307-17. doi: 10.1254/jjp.52.307.
We examined the effect of thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on bronchoconstriction induced by antigen and various spasmogenic mediators in guinea pigs in vivo. Further, inhibitory activities of OKY-046 on contractions of isolated tracheae and lung parenchymal strips induced by various contractile agents were also investigated in vitro. OKY-046, but not indomethacin, significantly inhibited antigen-induced bronchoconstriction in a dose-dependent manner. Moreover, OKY-046 attenuated bronchoconstrictions induced by peptide leukotrienes (LTs) and platelet activating factor (PAF), but not those by histamine, prostaglandin D2 (PGD2) and STA2 (a stable TXA2 mimetic agent). Although contractile responses induced by spasmogens such as peptide LTs, PAF and histamine were not influenced by OKY-046 in isolated tracheae, OKY-046 elicited significant and concentration-dependent inhibitions against contractile responses induced by peptide LTs and PAF in isolated lung parenchymal strips. These results suggest the possible involvement of TXA2 in the development of anaphylactic bronchoconstriction in sensitized guinea pigs.
我们在豚鼠体内研究了血栓素A2（TXA2）合成酶抑制剂OKY-046对抗原及多种致痉介质诱导的支气管收缩的影响。此外，还在体外研究了OKY-046对多种收缩剂诱导的离体气管和肺实质条收缩的抑制活性。OKY-046而非吲哚美辛能以剂量依赖的方式显著抑制抗原诱导的支气管收缩。此外，OKY-046可减轻肽白三烯（LTs）和血小板活化因子（PAF）诱导的支气管收缩，但对组胺、前列腺素D2（PGD2）和STA2（一种稳定的TXA2模拟剂）诱导的支气管收缩无作用。虽然在离体气管中，肽LTs、PAF和组胺等致痉剂诱导的收缩反应不受OKY-046影响，但OKY-046对离体肺实质条中肽LTs和PAF诱导的收缩反应有显著的浓度依赖性抑制作用。这些结果提示TXA2可能参与致敏豚鼠过敏性支气管收缩的发生。
