Fukushima C, Shimoda T, Matsuse H, Takao A, Sakai H, Asai S, Kohno S, Hara K
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Ann Allergy Asthma Immunol. 1996 Dec;77(6):483-7. doi: 10.1016/S1081-1206(10)63355-8.
Several mediators are released from mast cells during allergic reactions. These substances cause contraction of airway smooth muscles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A2 (TXA2) has a particularly strong bronchoconstrictive effect.
We examined antigen-induced contraction of excised human lungs and the suppressive effects of TXA2 synthetase inhibitor on TXA2 release.
Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus baths, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA2 synthetase, were added. Following the measurement of TXB2 and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of TXB2 and LT was measured after contraction.
Antigen-induced release of TXB2 was significantly suppressed by DP-1904 in a concentration-dependent manner. DP-1904 did not inhibit parenchymal contraction and the release of LT.
Antigen-induced parenchymal contraction was not suppressed by inhibition of TXA2 release, suggesting that DP-1904 may not be effective in asthma.
在过敏反应期间，几种介质从肥大细胞释放。这些物质会导致气道平滑肌收缩、增加血管通透性并增强黏液分泌。在这些介质中，血栓素A2（TXA2）具有特别强的支气管收缩作用。
我们研究了抗原诱导的离体人肺收缩以及TXA2合成酶抑制剂对TXA2释放的抑制作用。
用人血清对螨的5+RAST效价的人肺实质条进行被动致敏。将它们悬挂在马格努斯浴槽中，向其中加入缓冲液和10（-4）至10（-8）M的TXA2合成酶抑制剂DP-1904。在测量每个浴槽中TXB2和白三烯（LT）的浓度后，通过添加螨抗原诱导实质收缩。收缩后测量TXB2和LT的浓度。
DP-1904以浓度依赖性方式显著抑制抗原诱导的TXB2释放。DP-1904不抑制实质收缩和LT释放。
抑制TXA2释放并未抑制抗原诱导的实质收缩，这表明DP-1904可能对哮喘无效。
