Johnson R M, Lincoln T M
Mol Pharmacol. 1985 Mar;27(3):333-42.
The effects of nitroprusside (NP), glyceryl trinitrate (GTN), and the 8-bromo analog of cyclic GMP (8-Br-cGMP) on norepinephrine (NE)-stimulated phosphorylase a formation and myosin light chain (MLC) phosphorylation were examined in the rat aorta. NE produced a time-dependent increase in tension, phosphorylase a formation, and MLC phosphorylation. The formation of phosphorylase a and phosphorylation of MLC were transient, since both processes declined to basal levels within 30 min after the addition of NE even though tension remained elevated. NP and GTN inhibited tension, phosphorylase a formation, and MLC phosphorylation although inhibition of phosphorylase was greater when strips were treated with submaximal (i.e., 0.01 microM) NE concentrations. GTN was a more effective inhibitor of phosphorylase a formation than NP in NE-treated strips, although both agents and 8-Br-cGMP inhibited MLC phosphorylation. The guanylate cyclase inhibitor methylene blue (10 microM) effectively prevented the effects of NP and GTN. The results suggest that NP, GTN, and 8-Br-cGMP inhibit phosphorylase kinase and MLC kinase activation by lowering Ca2+ in the cell. This hypothesis is supported by the observations that 8-Br-cGMP inhibited the Ca2+-dependent, KCl-induced phosphorylase a formation most markedly at reduced concentrations of extra-cellular Ca2+. In addition, neither NP, GTN, nor 8-Br-cGMP inhibited phosphorylase a formation in forskolin-treated tissues, which occurred in response to cAMP-dependent phosphorylation of phosphorylase b kinase.
在大鼠主动脉中研究了硝普钠（NP）、硝酸甘油（GTN）和环鸟苷酸（cGMP）的8-溴类似物（8-Br-cGMP）对去甲肾上腺素（NE）刺激的磷酸化酶a形成和肌球蛋白轻链（MLC）磷酸化的影响。NE使张力、磷酸化酶a形成和MLC磷酸化呈时间依赖性增加。磷酸化酶a的形成和MLC的磷酸化是短暂的，因为即使张力仍然升高，在添加NE后30分钟内这两个过程都降至基础水平。NP和GTN抑制张力、磷酸化酶a形成和MLC磷酸化，尽管当条带用次最大（即0.01 microM）NE浓度处理时，对磷酸化酶的抑制作用更大。在NE处理的条带中，GTN比NP更有效地抑制磷酸化酶a的形成，尽管这两种药物和8-Br-cGMP都抑制MLC磷酸化。鸟苷酸环化酶抑制剂亚甲蓝（10 microM）有效地阻止了NP和GTN的作用。结果表明，NP、GTN和8-Br-cGMP通过降低细胞内Ca2+来抑制磷酸化酶激酶和MLC激酶的激活。这一假设得到以下观察结果的支持：在细胞外Ca2+浓度降低时，8-Br-cGMP最明显地抑制了Ca2+依赖性、KCl诱导的磷酸化酶a形成。此外，NP、GTN和8-Br-cGMP均未抑制福斯高林处理组织中的磷酸化酶a形成，该形成是由磷酸化酶b激酶的cAMP依赖性磷酸化引起的。
