Ohuchi K, Takahashi C, Hirasawa N, Watanabe M, Fujiki H, Tsurufuji S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Biochim Biophys Acta. 1989 May 15;1003(1):9-14. doi: 10.1016/0005-2760(89)90091-x.
Thapsigargin, a non-TPA-type tumor promoter, releases histamine and stimulates arachidonic acid metabolism in rat peritoneal mast cells. In order to clarify the relationship between the histamine-releasing activity and the arachidonic acid metabolism-stimulating activity of thapsigargin in mast cells, the effects of cyclooxygenase inhibitors, indomethacin and ibuprofen, a lipoxygenase inhibitor, AA861, and dual inhibitors for cyclooxygenase and lipoxygenase, nordihydroguaiaretic acid and BW755C, on histamine release and arachidonic acid metabolism were examined. High-performance liquid chromatography analysis revealed that the peritoneal mast cells preferentially produce prostaglandin D2 by thapsigargin treatment. These inhibitors suppressed thapsigargin-induced prostaglandin D2 production in a dose-dependent manner, but failed to inhibit histamine release, suggesting that the mechanisms for stimulation of histamine release by thapsigargin is not dependent on increased arachidonic acid metabolism. Time-course experiments of histamine release and the release of radioactivity from [3H]arachidonic acid-labeled mast cells also provide evidence for a difference in mechanism.
毒胡萝卜素是一种非TPA类型的肿瘤促进剂，可释放组胺并刺激大鼠腹膜肥大细胞中的花生四烯酸代谢。为了阐明毒胡萝卜素在肥大细胞中的组胺释放活性与花生四烯酸代谢刺激活性之间的关系，研究了环氧化酶抑制剂吲哚美辛和布洛芬、脂氧合酶抑制剂AA861以及环氧化酶和脂氧合酶双重抑制剂去甲二氢愈创木酸和BW755C对组胺释放和花生四烯酸代谢的影响。高效液相色谱分析表明，腹膜肥大细胞经毒胡萝卜素处理后优先产生前列腺素D2。这些抑制剂以剂量依赖的方式抑制毒胡萝卜素诱导的前列腺素D2产生，但未能抑制组胺释放，这表明毒胡萝卜素刺激组胺释放的机制不依赖于花生四烯酸代谢的增加。组胺释放的时间进程实验以及来自[3H]花生四烯酸标记肥大细胞的放射性释放实验也为机制上的差异提供了证据。
