Chuang A T, Strauss J D, Steers W D, Murphy R A
Department of Urology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Life Sci. 1998;63(3):185-94. doi: 10.1016/s0024-3205(98)00259-8.
We tested the prevailing paradigm that relaxation of corpus cavernosum smooth muscle (CCSM) and penile erection depends upon nitric oxide-induced elevation of myoplasmic cGMP and reduced Ca2+-dependent myosin regulatory light chain phosphorylation levels. This hypothesis invokes a reversal of normal activation pathways. Upon stimulation with 250 microM phenylephrine, phosphorylation of the 20 kD myosin regulatory light chains of rabbit or human CCSM increased approximately 4-fold coincident with contraction. Removal of the agonist was followed by a slow reduction in cross-bridge phosphorylation and force to basal levels. The NO donor, sodium nitroprusside elicited a dose-dependent increase in tissue [cGMP] associated with a rapid relaxation in the continued presence of phenylephrine, although cross-bridge phosphorylation remained significantly elevated. Thus the NO-cGMP inhibitory pathway in CCSM is not simply a reversal of excitatory signal transduction mechanisms. An unidentified mechanism contributes to relaxation by decreasing the rate of cross-bridge recruitment through phosphorylation.
我们测试了当前的范式，即海绵体平滑肌（CCSM）的舒张和阴茎勃起依赖于一氧化氮诱导的肌浆cGMP升高以及降低的钙依赖性肌球蛋白调节轻链磷酸化水平。该假设引发了正常激活途径的逆转。用250微摩尔苯肾上腺素刺激后，兔或人CCSM的20 kD肌球蛋白调节轻链的磷酸化增加了约4倍，同时伴有收缩。去除激动剂后，横桥磷酸化和张力缓慢降低至基础水平。一氧化氮供体硝普钠引起组织中[cGMP]的剂量依赖性增加，与在苯肾上腺素持续存在下的快速舒张相关，尽管横桥磷酸化仍显著升高。因此，CCSM中的一氧化氮 - cGMP抑制途径并非简单地是兴奋性信号转导机制的逆转。一种未知机制通过磷酸化降低横桥募集速率来促进舒张。
