Tamaoki J, Takemura H, Tagaya E, Sakai A, Yamawaki I, Konno K
First Department of Medicine, Tokyo Women's Medical College, Japan.
Eur J Pharmacol. 1995 May 15;278(2):161-6. doi: 10.1016/0014-2999(95)00114-z.
The effect of the anti-allergic drug azelastine, 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4-yl)-1-(2H)-phth alazione), on airway hyperresponsiveness induced by immunologically stimulated pulmonary alveolar macrophages was investigated in canine bronchial segments under isometric conditions in vitro. Macrophages stimulated with anti-dinitrophenyl immunoglobulin E (IgE) antibody and dinitrophenyl-human serum albumin potentiated the contractile responses to electrical field stimulation at all frequencies, an effect that was abolished by azelastine (3 x 10(-5) M). In contrast, azelastine had no effect on the potentiation of the contractile responses to electrical stimulation by U46619, a thromboxane A2 mimetic. The IgE-mediated release of thromboxane A2 from macrophages was inhibited by azelastine in a concentration-dependent fashion, the maximal decrease and the concentration required to produce a half-maximal effect being 84 +/- 6% (P < 0.001) and 16 microM, respectively. These results suggest that azelastine may attenuate macrophage-induced parasympathetic airway hyperresponsiveness through an inhibition of the release of thromboxane A2.
在体外等长条件下，研究了抗组胺药氮卓斯汀（4-（对氯苄基）-2-（六氢-1-甲基-1H-氮杂卓-4-基）-1（2H）-酞嗪酮）对免疫刺激的肺泡巨噬细胞诱导的犬支气管节段气道高反应性的影响。用抗二硝基苯基免疫球蛋白E（IgE）抗体和二硝基苯基人血清白蛋白刺激的巨噬细胞增强了在所有频率下对电场刺激的收缩反应，氮卓斯汀（3×10⁻⁵M）可消除这种作用。相比之下，氮卓斯汀对血栓素A2模拟物U46619增强的电刺激收缩反应没有影响。氮卓斯汀以浓度依赖性方式抑制巨噬细胞中血栓素A2的IgE介导释放，最大降低率和产生半数最大效应所需的浓度分别为84±6%（P<0.001）和16μM。这些结果表明，氮卓斯汀可能通过抑制血栓素A2的释放来减轻巨噬细胞诱导的副交感神经气道高反应性。
