Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Biochem Biophys Res Commun. 2014 May 30;448(2):236-40. doi: 10.1016/j.bbrc.2014.04.099. Epub 2014 Apr 30.
Intact HEK293 cells and B103 neuroblastoma cells possess high basal concentrations of the established second messengers cAMP and cGMP and of the emerging second messengers cCMP and cUMP. We asked the question which nucleotidyl cyclase accounts for the high basal cNMP concentrations. Activators and inhibitors of soluble guanylyl cyclase had no major effects on cNMPs, and the activator of membranous adenylyl cyclase forskolin increased only cAMP. Addition of bicarbonate to medium increased, whereas removal of bicarbonate decreased levels of all four cNMPs. The inhibitor of soluble adenylyl cyclase, 2-(1H-benzo[d]imidazol-2-ylthio)-N'-(5-bromo-2-hydroxybenzylidene) propanehydrazide (KH7), reduced bicarbonate-stimulated cNMPs. In conclusion, bicarbonate-stimulated soluble adenylyl cyclase plays an important role in the regulation of basal cellular cNMP levels, most notably cCMP and cUMP.
完整的 HEK293 细胞和 B103 神经母细胞瘤细胞具有高浓度的基础第二信使 cAMP 和 cGMP,以及新兴的第二信使 cCMP 和 cUMP。我们提出了这样一个问题,即哪种核苷酸环化酶负责产生高浓度的基础 cNMP。可溶性鸟苷酸环化酶的激活剂和抑制剂对 cNMP 没有重大影响,而膜结合的腺苷酸环化酶的激活剂 forskolin 仅增加 cAMP。碳酸氢盐的添加增加了所有四种 cNMP 的水平,而碳酸氢盐的去除则降低了它们的水平。可溶性腺苷酸环化酶的抑制剂 2-(1H-苯并[d]咪唑-2-基硫代)-N'-(5-溴-2-羟基苯亚甲基)丙烷脒(KH7)降低了碳酸氢盐刺激的 cNMP。总之,碳酸氢盐刺激的可溶性腺苷酸环化酶在调节基础细胞 cNMP 水平方面起着重要作用,尤其是 cCMP 和 cUMP。