Sowa G, Przewłocki R
Neuropeptide Research Department, Polish Academy of Sciences, Kraków, Poland.
Br J Pharmacol. 1995 Sep;116(2):1711-2. doi: 10.1111/j.1476-5381.1995.tb16649.x.
Staurosporine (3-100 nM), frequently used as a protein kinase C (PKC) inhibitor, increased accumulation of nitrite in the culture medium of rat peritoneal macrophages up to 6 times above the control level. Moreover, when used in combination with the stable analogue of cyclic AMP, dibutyrylcyclic AMP (db cyclic AMP; 0.1 mM), and/or a cytokine, tumour necrosis factor-alpha (TNF alpha; 100 u ml-1), staurosporine synergistically potentiated, up to 30 times, nitrite accumulation. On the other hand, the other PKC inhibitors, calphostin C and H-7 (10 nM-10 microM) were not effective under the same conditions. The staurosporine-induced nitrite accumulation, in both the presence and the absence of TNF alpha and/or db cyclic AMP was effectively inhibited by the protein synthesis inhibitor, cycloheximide, or by the nitric oxide (NO) synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA). Thus our data suggest that staurosporine may enhance NO production in macrophages via intracellular mechanisms unrelated to the PKC inhibition.
星形孢菌素（3 - 100 nM）常被用作蛋白激酶C（PKC）抑制剂，它使大鼠腹腔巨噬细胞培养基中亚硝酸盐的积累量增加至对照水平的6倍以上。此外，当与环磷酸腺苷（cAMP）的稳定类似物二丁酰环磷腺苷（db cAMP；0.1 mM）和/或细胞因子肿瘤坏死因子-α（TNFα；100 u/ml）联合使用时，星形孢菌素可协同增强亚硝酸盐的积累，增幅高达30倍。另一方面，其他PKC抑制剂，如钙泊三醇C和H - 7（10 nM - 10 μM）在相同条件下无效。在有或没有TNFα和/或db cAMP的情况下，蛋白合成抑制剂环己酰亚胺或一氧化氮（NO）合成抑制剂NG - 单甲基 - L - 精氨酸（L - NMMA）均可有效抑制星形孢菌素诱导的亚硝酸盐积累。因此，我们的数据表明，星形孢菌素可能通过与PKC抑制无关的细胞内机制增强巨噬细胞中NO的产生。
