三环癸烷-9-基-黄原酸酯（D609）抑制吞噬细胞中一氧化氮合酶活性的诱导。
Induction of nitric oxide synthase activity in phagocytic cells inhibited by tricyclodecan-9-yl-xanthogenate (D609).
作者信息
Tschaikowsky K, Meisner M, Schönhuber F, Rügheimer E
机构信息
Institute of Anesthesiology, University of Erlangen-Nuremberg, Germany.
出版信息
Br J Pharmacol. 1994 Nov;113(3):664-8. doi: 10.1111/j.1476-5381.1994.tb17043.x.
Abstract
- The synthesis of nitric oxide (NO) by immune-stimulated murine phagocytic cells (J774) and the modulation of this synthesis by tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), was investigated. D609 dose-dependently suppressed production of NO, as measured by the release of nitrite and nitrate, in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in intact cultured cells with an IC50 of approximately 20 micrograms ml-1. D609 at 40 micrograms ml-1 completely abrogated immune-stimulated nitrite production. 2. The inhibitory effects of D609 on nitrite production were time-dependent and restricted to the first 18 h post-stimulation. D609 did not inhibit nitrite production in the cytosol of immune-stimulated phagocytes. 3. These findings indicate that the xanthogenate, D609, is a potent inhibitor of the induction of NO-synthase activity in immune-stimulated phagocytes. Furthermore, since D609 has been demonstrated to inhibit PC-PLC specifically, our findings suggest that the activation of this enzyme by LPS and IFN-gamma is a proximal step in the signal transduction of inducible NO-synthase in phagocytic cells.
摘要
- 研究了免疫刺激的小鼠吞噬细胞（J774）中一氧化氮（NO）的合成以及磷脂酰胆碱特异性磷脂酶C（PC-PLC）的特异性抑制剂三环癸烷-9-基黄原酸酯（D609）对该合成的调节作用。在完整的培养细胞中，通过亚硝酸盐和硝酸盐的释放来测量，D609对脂多糖（LPS）和干扰素-γ（IFN-γ）刺激产生的NO呈剂量依赖性抑制，其IC50约为20微克/毫升。40微克/毫升的D609完全消除了免疫刺激产生的亚硝酸盐。2. D609对亚硝酸盐产生的抑制作用具有时间依赖性，且仅限于刺激后的前18小时。D609不抑制免疫刺激吞噬细胞胞质溶胶中的亚硝酸盐产生。3. 这些发现表明，黄原酸酯D609是免疫刺激吞噬细胞中NO合酶活性诱导的有效抑制剂。此外，由于已证明D609能特异性抑制PC-PLC，我们的发现提示LPS和IFN-γ对该酶的激活是吞噬细胞中诱导型NO合酶信号转导的近端步骤。
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